Objective: After resuscitation, many patients die from post-cardiac arrest syndrome, partially driven by a cytokine storm. Restoring contractility of the heart is one of multiple factors affecting the outcome after extracorporeal cardiopulmonary resuscitation (ECPR). Therefore, we investigated the effect of cytokine adsorption on the left ventricular (LV) contractility of the heart after circulatory arrest (CA).

Methods: We induced circulatory arrest by global ischemia in a pig model. To exclude resuscitation-associated side effects, we explanted the hearts after CA and resuscitated them under fully controlled conditions in an isolated Langendorff-circuit with (^w/CytoS group; N=7) or without (^w/oCytoS group; N=7) use of a cytokine adsorber (CytoSorb, Cytosorbents). The circuit was primed with the blood of the pig, which was collected after global ischemia. After 5 h, we evaluated the LV contractility with a balloon. We also measured pressure-contractility-matching (PCM) with different coronary perfusion pressures (CPP). We performed cytokine profiling in both groups and determined the transcriptomic profile of LV myocardial samples using gene microarrays.

Results: In ^w/CytoS, LV end-systolic pressure (ESP: 160±13 vs. 103±15 mmHg; p=0.017), the maximal slope of pressure increment (dp/dt_max: 1941±164 vs. 854±139 mmHg/s; p<0.001) and maximal slope of pressure decrement (dp/dt_min: -1062±154 vs. -493±69 mmHg/s; p<0.05) were superior compared to ^w/oCytoS. PCM resulted in a significantly improved ESP (107±6 vs. 70±14 mmHg; p=0.032), dp/dt_max (1399±109 vs. 632±106 mmHg/s; p<0.001) and dp/dt_min (-729±176 vs. -372±46 mmHg/s, p=0.091) at 20 mmHg of CPP in ^w/CytoS compared to ^w/oCytoS. IL-1ra and IL-18 were decreased, INF-γ, IL-6, IL-8 and IL-12 were increased and IL-1β, TNF-α unaffected in ^w/CytoS. 25,470 genes were determined. In ^w/CytoS compared to ^w/oCytoS, 80 genes were upregulated, involved in the CD40/CD40L pathway and cytokine-storm related key regulators, and 40 genes were downregulated, involved in PI3K-Akt related pathways, inositol triphosphate receptor-mediated signaling for smooth muscle cell contraction and protein-tyrosine kinase receptors.

Conclusions: The use of CytoSorb during resuscitation of the heart and during the first hours of reperfusion after global circulatory arrest improves the systolic and diastolic function of the left ventricle and modifies the cytokine expression as well as transcriptomic profile.