Association of MMP-9 and TIMP-1 concentration with neurological outcome after cardiac arrest and resuscitation – a substudy of the COMACARE trial

Abstract

Background and aim Out-of-hospital cardiac arrest (OHCA) leads to an inflammatory response, including alterations in matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 concentrations. We investigated whether the MMP-9 and TIMP-1 plasma concentrations of OHCA patients are elevated and associated with outcome among OHCA patients. Methods This was a substudy of the prospective COMACARE trial (NCT02698917). We included 112 OHCA patients and measured MMP-9 and TIMP-1 concentrations at ICU admission, 24, 48 and at 72 h. Preoperative blood samples from 40 age- and sex-matched elective cardiac surgery patients were used as controls. We defined favourable outcome as a Cerebral Performance Category (CPC) 1–2 at six months. Results The median (interquartile range) MMP-9 concentrations at admission for OHCA patients and for controls were 369 (228–619) ng/mL and 66 (41–114) ng/mL, respectively, p < 0.001. The TIMP-1 concentrations for OHCA patients at admission and for controls were 137 (104–163) ng/mL and 79 (71–96) ng/mL, respectively, p < 0.001. The MMP-9 levels peaked at admission; 448 (241–700) ng/mL in patients with CPC ≥ 3 as compared with 340 (224–563) ng/mL in patients with CPC 1–2 ( p = 0.103). TIMP-1 concentrations peaked at 48 h; 223 (174–323) ng/mL in patients with CPC ≥ 3 as compared with 201 (148–273) ng/mL in patients with CPC 1–2 ( p = 0.104). In a logistic regression model, neither biomarker demonstrated association with outcome. Conclusion OHCA patients had higher plasma concentrations of MMP-9 and TIMP-1 than elective surgery patients. However, the concentrations showed no association with outcome.