PB1214 - Characterization of dynamic changes to fibrinolysis in porcine model of cardiac arrest

Background: Many survivors of an initial cardiac arrest develop disability and death, stemming from post-cardiac arrest syndrome (PCAS). Multiple organ failure, bleeding, and thromboembolic complications are common in PCAS, and these processes may be secondary to acquired coagulopathy due to shock and reperfusion injury during cardiac arrest. Shock dysregulates both coagulation and fibrinolysis, but neither process is directly treated in typical resuscitation strategies. Understanding the underlying mechanism and the timeline of the development of coagulopathy in PCAS may allow for new targets for early intervention.

Aims: To characterize the temporal changes to fibrinolytic state using an established pig model of cardiac arrest.

Methods: Six Yorkshire pigs were anaesthetised and intubated, had ventricular fibrillation (VF)-arrest induced by transvenous pacing, and were resuscitated per standard Advanced Cardiac Life Support (ACLS). Whole blood samples were collected into citrate at four times: baseline (Pre), intra-arrest (VF 1-min), post-arrest (VF 8-min), and death (PM). Isolated plasma was then subjected to a turbidimetric plasma clot lysis assay, whereby clots were generated using human thrombin (5 nM) and lysis was initiated using porcine tissue-type plasminogen activator (tPA; 10 nM). In addition, baseline OD readings and total change in turbidity signal were quantified as a surrogate for clot structure.

Results: Clot lysis profiles showed transient fibrinolysis resistance at VF 1-min that was subsequently normalized by VF 8-min on three of the animals. Clot structure signal (i.e. total OD change) was significantly elevated (p < 0.005) by 1.8-fold relative to Pre at VF 1-min for 5 of the 6 animals. Total OD were higher at VF 8-min and PM both by 1.3-fold relative to Pre, however were not statistically significant. One animal showed complete resistance to fibrinolysis at all time points.

Conclusion(s): Fibrinolysis can effectively be studied in large animal models. Fibrinolysis is transiently down-regulated during cardiac arrest and the clot structure remains altered.