Detecting Critical Transitions in the Human Innate Immune System Post-cardiac Surgery

Presbitero, Alva; Quax, Rick; Krzhizhanovskaya, Valeria V.; Sloot, Peter M. A.

Coronary artery bypass grafting with cardiopulmonary bypass activates the human innate immune system (HIIS) and invokes a vigorous inflammatory response that is systemic. This massive inflammatory reaction can contribute to the development of postoperative complications that could topple the state of the system from health to disease, or even to some extent, death. The body, after all, is in a state where majority of its immune cell populations have been depleted, and sometimes needs days or even longer to recuperate. To obtain a deeper understanding on how HIIS responds to complications after cardiac surgery, we perturb the immune system model that we have developed in an earlier work in-silico by adding another source of inflammation triggering moieties (ITMs) hours after surgery in various regimes. A critical transition occurs upon the addition of a critical concentration of ITMs when the insult is sustained for approximately 3 h – a total concentration that corresponds to the fatal concentration of ITMs documented in literature. By perturbing HIIS in-silico with additional sources of ITMs to mimic persistent and recurring episodes of post-surgery complications, we are able to specify under which conditions critical transitions occur in HIIS, as well as pinpoint important blood parameters that exhibit critical transitions in our model. More importantly, by applying early warning signals on the clinical trial data used to calibrate and validate HIIS model, we are able to detect blood parameters that exhibit critical transitions in patients who died post-surgery, where pro-inflammatory cytokines are deemed potential markers for critical transitions.