Epinephrine Exacerbates Myocyte Injury in a Porcine Model of Cardiac Arrest
Authors: Barbaccia Thomas , Allen Shannon E. , Granica Elaine , Young Rebeccah F. , Palka Beth A. , Canty John M. , Weil Brian R. 
Published: April 2020

Objective

Although circulating cardiac troponin (cTn) concentrations are often elevated in patients following resuscitation from cardiac arrest (CA), this finding is commonly attributed to myocyte injury caused by ongoing myocardial infarction (MI) and/or defibrillation during resuscitation. To determine whether measurable cTn elevations occur independently of these factors, we employed serial sampling of systemic and coronary venous blood to quantify cTn release in a porcine model of CA devoid of ongoing MI or multiple defibrillation attempts. In light of recent concerns regarding potential detrimental effects of epinephrine (EPI) in CA, cTn levels were compared in animals that were resuscitated with vs. without exogenous EPI.

Methods

Swine (n=41) were subjected to 7 min CA via electrical induction of ventricular fibrillation (VF) followed by cardiopulmonary resuscitation (CPR) with manual chest compressions and mechanical ventilation for up to 20 min. Biphasic defibrillation (200 J) was performed 1 min after the start of CPR and a subset of animals (n=10) received intravenous EPI (0.015 mg/kg) 1 min later. After return of spontaneous circulation (ROSC; defined as unassisted systolic blood pressure >80 mmHg for 1 min), animals were followed for up to 4 hours with serial blood sampling from the jugular vein and coronary sinus for assessment of cTnI via a porcine‐specific ELISA.

Results

Among the entire cohort, 1.2±0.1 defibrillator shocks were required to terminate VF, ROSC was achieved 175±7 seconds after the initiation of CPR, and 15 animals (38%) survived for the entire 4‐hour recovery period (2/10 with EPI, 13/31 without EPI). Despite the absence of ongoing MI or prolonged resuscitation efforts, a significant 5‐fold rise in coronary sinus (from 106±17 to 526±74 ng/L, p<0.01) and systemic (from 67±14 to 350±54 ng/L, p<0.01) cTnI concentrations was observed 15 min post‐ROSC (trans‐coronary cTnI gradient from 39±7 to 176±29 ng/L, p<0.01). Widening of the trans‐coronary cTnI gradient continued throughout the recovery period, reaching 795±164 ng/L 4 hours post‐ROSC and leading to a 16‐fold increase in circulating cTnI concentrations at this timepoint (1087±208 ng/L, p<0.01 vs. baseline). Exogenous EPI exacerbated myocyte injury, as EPI‐treated animals exhibited a significantly higher trans‐coronary cTnI gradient 30 min post‐ROSC that persisted throughout the recovery period and led to significantly higher circulating cTnI concentrations vs. animals resuscitated without EPI at each timepoint (Figure
).

Conclusions

These results demonstrate that resuscitation from CA is associated with measurable elevations in cTnI as early as 15 min post‐ROSC, even in the absence of ongoing MI or prolonged CPR with multiple defibrillator shocks. Thus, assessment of circulating cTnI following resuscitation from CA is unlikely to accurately identify patients suffering from an acute coronary syndrome. Administration of exogenous EPI during resuscitation exacerbates the extent of myocyte injury, which may contribute to poor long‐term outcomes.

Support or Funding Information

Funding Sources

NIH, AHA, ZOLL Foundation, Pro‐Al Medico Technologies, Inc., UB CAT, NCATS, and the Dept. of Veterans Affairs.

Figure 1