Correlation of NLRP3 With Cognitive Dysfunction Early After Heart Valve Replacement Surgery

NCT04191642 | Completed

• 1 other identifier: Magang2018-020
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators decided to assess the prognostic value of NLRP3 inflammasome level in early after heart valve replacement surgery and whether it was related to postoperative cognitive dysfunction. Study population included 90 subjects. Neuropsychological tests were administrated one day before surgery and seven days after surgery. Before induction of anesthesia, before the end of the operation, 7 days after the operation, peripheral venous blood was sampled to measure IL-1B, IL-18 and NLRP3 inflammatory protein expression in peripheral blood monocytes. Analyze the data and draw conclusions.

Conditions

Inflammasomes; Cognitive Dysfunction; Pyrin Domain-Containing 3 Protein; Postoperative Complications

Keywords

Inflammasomes; Interleukin-18; Interleukin-1; NLR Family, Pyrin Domain-Containing 3 Protein; Postoperative cognitive dysfunction

Outcome Measures

Primary Outcomes (1)

• The correlation between peripheral blood NLRP3 inflammasome level and incidence of postoperative cognitive dysfunction

  Peripheral venous blood was sampled to measure NLRP3 inflammasome expression. POCD was defined by Z scores that based on the neuropsychological tests, and then, get the incidence of POCD. The method of Z scores is as follows: A patient was defined as having POCD when two Z scores in individual tests or the combined Z score were 1.96 or more. Neuropsychological tests included MMSE(screening method); Trail Making (A/B); Stroop Color-Word; Rey Auditory Verbal Learning Test; WAIS Digit Symbol Substitution Test; WAIS Digit Span; Verbal fluency test. Preoperative scores were compared with postoperative test results, subtracted the average practice effect from these changes, and then divided the result by the control-subject SD to obtain a Z score for each test. The Z scores of all tests in an individual patient were then summarized and divided by the SD for this sum of Z scores in the control subjects, creating a combined Z score.

  The day before surgery, 7 days after surgery

Secondary Outcomes (2)

• The correlation between peripheral blood IL-1B levels and incidence of postoperative cognitive dysfunction

  At the end of the surgery, 7 days after surgery

• The correlation between peripheral blood IL-18 levels and incidence of postoperative

  At the end of the surgery, 7 days after surgery

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Elderly heart surgery patients

You may qualify if:

• Patients were included if they had an American Society of Anesthesiologists status of II or III and older than 60 years old.

You may not qualify if:

• A preoperative history of liver or kidney dysfunction, peripheral vascular disease, diabetes mellitus, or arterial hypertension;
• Ischemic cerebrovascular disease;
• A history of an acute or evolving myocardial infarction or presentation with a left ventricular ejection fraction (LVEF) of less than 45%;
• Obesity (body mass index 430 kg/m2);
• Moderate or severe atherosclerotic lesions in the ascending aorta or carotid artery stenosis confirmed by preoperative ultrasonography
• Patients requiring re-exploration after surgery or a total CPB time more than 115 min
• Patients requiring highdose pharmacologic support (phenylephrine 4 100 mg bolus, or epinephrine 4 0.1mg/kg/min or both) to maintain hemodynamic stability (mean arterial pressure \[MAP\] more than 60 mmHg)

Sponsors & Collaborators

• General Hospital of Ningxia Medical University: lead

Study Sites (1)

Department of Anesthesiology, General Hospital of Ningxia Medical University

Yinchuan, Ningxia, 750004, China

Location

Related Publications (10)

• Afrasyab A, Qu P, Zhao Y, Peng K, Wang H, Lou D, Niu N, Yuan D. Correlation of NLRP3 with severity and prognosis of coronary atherosclerosis in acute coronary syndrome patients. Heart Vessels. 2016 Aug;31(8):1218-29. doi: 10.1007/s00380-015-0723-8. Epub 2015 Aug 20.

  PMID: 26290166 RESULT

• Meital LT, Coward AS, Windsor MT, Bailey TG, Kuballa A, Russell FD. A simple and effective method for the isolation and culture of human monocytes from small volumes of peripheral blood. J Immunol Methods. 2019 Sep;472:75-78. doi: 10.1016/j.jim.2019.04.005. Epub 2019 Jun 20.

  PMID: 31229469 RESULT

• Lenart N, Brough D, Denes A. Inflammasomes link vascular disease with neuroinflammation and brain disorders. J Cereb Blood Flow Metab. 2016 Oct;36(10):1668-1685. doi: 10.1177/0271678X16662043. Epub 2016 Aug 2.

  PMID: 27486046 RESULT

• Feinkohl I, Winterer G, Spies CD, Pischon T. Cognitive Reserve and the Risk of Postoperative Cognitive Dysfunction. Dtsch Arztebl Int. 2017 Feb 17;114(7):110-117. doi: 10.3238/arztebl.2017.0110.

  PMID: 28302254 RESULT

• Cao XZ, Ma H, Wang JK, Liu F, Wu BY, Tian AY, Wang LL, Tan WF. Postoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Dec 1;34(8):1426-32. doi: 10.1016/j.pnpbp.2010.07.027. Epub 2010 Aug 4.

  PMID: 20691747 RESULT

• Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS, Maze M. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010 Sep;68(3):360-8. doi: 10.1002/ana.22082.

  PMID: 20818791 RESULT

• Song L, Pei L, Yao S, Wu Y, Shang Y. NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies. Front Cell Neurosci. 2017 Mar 9;11:63. doi: 10.3389/fncel.2017.00063. eCollection 2017.

  PMID: 28337127 RESULT

• Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg. 1995 May;59(5):1289-95. doi: 10.1016/0003-4975(95)00106-u. No abstract available.

  PMID: 7733754 RESULT

• Rudolph JL, Schreiber KA, Culley DJ, McGlinchey RE, Crosby G, Levitsky S, Marcantonio ER. Measurement of post-operative cognitive dysfunction after cardiac surgery: a systematic review. Acta Anaesthesiol Scand. 2010 Jul;54(6):663-77. doi: 10.1111/j.1399-6576.2010.02236.x. Epub 2010 Apr 15.

  PMID: 20397979 RESULT

• Ma G, Sun P, Chen Y, Jiang X, Zhang C, Qu B, Meng X. NLRP3 inflammasome activation contributes to the cognitive decline after cardiac surgery. Front Surg. 2022 Nov 2;9:992769. doi: 10.3389/fsurg.2022.992769. eCollection 2022.

  PMID: 36406365 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Before induction of anesthesia, at the end of the operation, 7 days after the operation, peripheral venous blood was sampled to measure IL-1B, IL-18 and NLRP3 inflammatory protein expression in peripheral blood monocytes.

MeSH Terms

Conditions

Cognitive Dysfunction; Postoperative Complications; Postoperative Cognitive Complications

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gang Ma, doctor

  Department of Anesthesiology General Hospital of Ningxia Medical University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2019
• First Posted: December 10, 2019
• Study Start: April 1, 2019
• Primary Completion: January 30, 2021
• Study Completion: January 30, 2021
• Last Updated: September 1, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)