A comparison of etanercept vs. infliximab for the treatment of post-arrest myocardial dysfunction in a swine model of ventricular fibrillation

Abstract

Aims: To compare the effects of two TNF-α antagonists, etanercept and infliximab, on post-cardiac arrest hemodynamics and global left ventricular function (LV) in a swine model following ventricular fibrillation (VF).

Methods: Domestic swine (n=30) were placed under general anesthesia and instrumented before VF was induced electrically. After 7 min of VF, standard ACLS resuscitation was performed. Animals achieving return of spontaneous circulation (ROSC) were randomized to immediately receive infliximab (5 mg/kg, n=10) or etanercept (0.3 mg/kg [4 mg/m(2)], n=10) or vehicle (250 mL normal saline [NS], n=10) and LV function and hemodynamics were monitored for 3 h.

Results: Following ROSC, mean arterial pressure (MAP), stroke work (SW), and LV dP/dt fell from pre-arrest values in all groups. However, at the 30 min nadir, infliximab-treated animals had higher MAP than either the NS group (difference 14.4 mm Hg, 95% confidence interval [CI] 4.2-24.7) or the etanercept group (19.2 mm Hg, 95% CI 9.0-29.5), higher SW than the NS group (10.3 gm-m, 95% CI 5.1-15.5) or the etanercept group (8.9 gm-m, 95% CI 4.0-14.4) and greater LV dP/dt than the NS group (282.9 mm Hg/s, 95% CI 169.6-386.1 higher with infliximab) or the etanercep group (228.9 mm Hg/s, 95% CI 115.6-342.2 higher with infliximab).

Conclusions: Only infliximab demonstrated a beneficial effect on post cardiac arrest hemodynamics and LV function in this swine model. Etanercept was no better in this regard than saline.

Figure 1

Mean natural log transformed values for TNF-alpha levels between animals administered infliximab, etanercept, or saline in a swine model of ischemic VF (original scale in pg/mL). *Adjusted p<0.05 for comparison with pre-arrest values.

Figure 2

Mean arterial pressure (MAP) measured during the first three hours post-ROSC in animals administered infliximab, etanercept, or placebo. a) p<0.05 for infliximab/saline comparison, b) p<0.05 for infliximab/etanercept comparison

Figure 3

Mean Left Ventricular Stroke Work (SW) as measured during the first three hours post-ROSC in animals administered infliximab, etanercept, or placebo. a) p<0.05 for infliximab/saline comparison, b) p<0.05 for infliximab/etanercept comparison

Figure 4

Tau measured during the first three hours post-ROSC in animals administered infliximab, etanercept, or placebo. *p<0.05 for differences between infliximab and saline.