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

Q: What was the main objective of this substudy?

To determine whether plasma MMP-9 and TIMP-1 concentrations in OHCA patients are elevated and whether they relate to neurological outcome after cardiac arrest and resuscitation.

Q: How were MMP-9 and TIMP-1 measured, and when were samples collected?

MMP-9 and TIMP-1 concentrations were measured in 112 OHCA patients at ICU admission and at 24, 48, and 72 hours.

Q: Did MMP-9 or TIMP-1 concentrations predict neurological outcome?

No. Logistic regression showed that neither biomarker demonstrated an association with neurological outcome.

Sep 29, 2026

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Out-of-hospital cardiac arrest (OHCA) triggers an inflammatory response that includes altered concentrations of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1. Plasma levels of MMP-9 and TIMP-1 were measured in 112 OHCA patients at ICU admission and at 24, 48, and 72 hours, with 40 elective cardiac surgery patients as controls. MMP-9 and TIMP-1 were elevated after OHCA but showed no association with six-month neurological outcome.

LanguageEnglish

CategoryResearch & Report

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R E S U S C I T A T I O N P L U S 27 (20 26) 1011 87 Original Article Association of MMP-9 and TIMP-1 concentration with neurological outcome after cardiac arrest and resuscitation – a substudy of the COMACARE trial Emilia Kortesuo a,*, Joonas Tirkkonena,b, Matti Reinikainenc, Pirkka T. Pekkarinend, Eeva Moilanena,e, Liisa Pet¨aj¨ad, Markus B Skrifvarsd, Johanna H¨astbackaa,b 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/mLand 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. Keywords: Out-of-hospital cardiac arrest, OHCA, MMP-9, TIMP-1, Inﬂammation Introduction Cardiac arrest leads to sudden loss of circulation and causes ischemia to which especially the central nervous system is sensitive.1 After successful resuscitation from cardiac arrest, a multi-organ dysfunction called post-cardiac arrest syndrome (PCAS) occurs in some patients.2 It is likely caused by multiple factors, but inﬂammatory response resembling septic shock, following whole-body ischemia and reperfusion at return of spontaneous circulation (ROSC), plays a substantial part.3 Therefore, inﬂammatory biomarkers are interesting regarding the development of organ dysfunction and brain injury.4,5 After out-of-hospital cardiac arrest (OHCA), blood concentrations of matrix metalloproteinase (MMP)-9 are increased,6 but their role has not been properly investigated. In a previous study, MMP-9 and TIMP-1 concentrations were compared between patients treated with therapeutic hypothermia and a control group without targeted temperature management.6 The main ﬁnding was that MMP-9 levels decreased during hypothermia but increased again after rewarming. However, only two sampling time points were available, and no admission samples were collected. In addition, the study lacked a control group with underlying cardiovascular pathology, which would have been important for assessing the magnitude of MMP-9 and TIMP-1 changes during acute global ischaemia.6 MMPs are a group of zinc-dependent endopeptidases with collagen cleaving capability * Corresponding author. E-mail address: emilia. kortesuo@tuni.ﬁ (E. Kortesuo) . [https://doi.org/10.1016/j.resplu.2025.101187](https://doi.org/10.1016/j.resplu.2025.101187) Received 5 September 2025; Received in revised form 30 November 2025; Accepted 2 December 2025 2666-5204/􀀁 2025 The Authors. Published by Elsevier B.V. This is an open access article under

FAQs

What was the main objective of this substudy?

To determine whether plasma MMP-9 and TIMP-1 concentrations in OHCA patients are elevated and whether they relate to neurological outcome after cardiac arrest and resuscitation.

How were MMP-9 and TIMP-1 measured, and when were samples collected?

MMP-9 and TIMP-1 concentrations were measured in 112 OHCA patients at ICU admission and at 24, 48, and 72 hours.

Did MMP-9 or TIMP-1 concentrations predict neurological outcome?

No. Logistic regression showed that neither biomarker demonstrated an association with neurological outcome.

Sep 29, 2026

Upload by Angel