Impact of mild therapeutic hypothermia on plasma markers of inflammation and apoptosis in non-resuscitated patients with acute myocardial infarction and cardiogenic shock.

Background: Patients with cardiogenic shock (CS) following acute myocardial infarction (AMI) are challenged by pro-inflammatory and pro-apoptotic cellular processes. Little is known about the effect of mild therapeutic hypothermia (MTH) on these alterations.

Methods: Blood plasma from 40 patients included in the randomized SHOCK-COOL trial, which compared MTH (33 °C) versus no hypothermia in AMI-CS without cardiac arrest, from the first 3 days of hospitalization was used to determine interleukins (IL)-6 and IL-1β, tumor necrosis factor-alpha (TNF-α), intercellular and vascular soluble adhesion molecules (ICAM1 and VCAM1), TNF-receptor 1 (TNF-R1), TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), soluble FAS-ligand (sFASL), and soluble FAS (sFAS). These markers were also determined in 11 healthy controls.

Results: All markers except for TNF-R1 and sFASL reached their highest levels on day two or day three in both CS groups. IL-1β and sFAS reached higher maximum levels in the MTH group. IL-1β was higher in the MTH group on day 2 (+ 38%, p = 0.014) and on day 3 (+ 9%, p = 0.047), but the averaged group-wise individual maxima were comparable (24 [17-30] versus 20 [12-25], p = 0.138). The pro-apoptotic marker sFAS was also higher in the MTH group on day 2 (+ 85%, p = 0.004) and day 3 (+ 170%, p < 0.001); the averaged individual maxima were significantly higher in the MTH group (25 [15-38] versus 15 [10-21] ng/ml, p = 0.008).

Conclusions: Hypothermia in AMI-CS without cardiac arrest has no moderating effect on the assessed pro-inflammatory cytokines. However, sFAS showed significantly higher individual peak maxima in the MTH group indicating enhancement of pro-apoptotic mechanisms via the soluble FAS/FASL pathway.