schliessen

Filtern

 

Bibliotheken

Pexelizumab fails to inhibit assembly of the terminal complement complex in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Insight from a substudy of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial

Background Reasons for pexelizumab lack of benefit in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention remain unclear. In a substudy of the APEX-AMI trial, we explored the hypothesis that early complement activation preceding drug administration expla... Full description

Journal Title: The American heart journal 2012, Vol.164 (1), p.43-51
Main Author: Martel, Catherine, PhD
Other Authors: Granger, Christopher B., MD , Ghitescu, Marta, MS , Stebbins, Amanda, MS , Fortier, Annik, MS , Armstrong, Paul W., MD , Bonnefoy, Arnaud, PhD , Theroux, Pierre, MD
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: New York, NY: Mosby, Inc
ID: ISSN: 0002-8703
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_proquest_miscellaneous_1026695837
title: Pexelizumab fails to inhibit assembly of the terminal complement complex in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Insight from a substudy of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial
format: Article
creator:
  • Martel, Catherine, PhD
  • Granger, Christopher B., MD
  • Ghitescu, Marta, MS
  • Stebbins, Amanda, MS
  • Fortier, Annik, MS
  • Armstrong, Paul W., MD
  • Bonnefoy, Arnaud, PhD
  • Theroux, Pierre, MD
subjects:
  • Abridged Index Medicus
  • Aged
  • Analysis
  • Angioplasty, Balloon, Coronary
  • Antibodies, Monoclonal, Humanized - therapeutic use
  • Apoptosis
  • Biological and medical sciences
  • Cardiac patients
  • Cardiology. Vascular system
  • Cardiovascular
  • Care and treatment
  • Cell culture
  • Complement Membrane Attack Complex - antagonists & inhibitors
  • Coronary heart disease
  • Diseases of the cardiovascular system
  • Double-Blind Method
  • Female
  • Heart
  • Heart attack
  • Heart attacks
  • Humans
  • Male
  • Medical sciences
  • Middle Aged
  • Mortality
  • Myocardial Infarction - therapy
  • Myocarditis. Cardiomyopathies
  • Prospective Studies
  • Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
  • Single-Chain Antibodies - therapeutic use
  • Transluminal angioplasty
  • Treatment Failure
ispartof: The American heart journal, 2012, Vol.164 (1), p.43-51
description: Background Reasons for pexelizumab lack of benefit in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention remain unclear. In a substudy of the APEX-AMI trial, we explored the hypothesis that early complement activation preceding drug administration explained the failure. Methods A panel of terminal complement complex proteins and fragments and biomarkers of inflammation, apoptosis, and high-risk features were assessed in serum obtained before and 24 hours after administration of placebo or pexelizumab and primary percutaneous coronary intervention (n = 356) and in human umbilical vein endothelial cell cultures coincubated with serum (n = 45). Results In the placebo group, C5a and sC5b-9 levels increased by 37% (7.9-14.2 ηg/mL, P = .007) and 96% (442-845 ηg/mL, P < .0001), respectively, during the first 24 hours. Pexelizumab prevented the increase in C5a ( P = .01 vs placebo), but not that of sC5b-9 (502-1,157 ηg/mL, not significant vs placebo). Levels of C-reactive protein, interleukin (IL) 6, IL-1ß, Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) or Chemokine C-C motif ligand 5 (CCL5), and N-terminal probrain natriuretic peptide increased significantly in both groups; those of IL-10, IL-12, IL-1ra, and Interferon gamma-induced protein 10 (IP-10) or C-X-C motif chemokine 10 (CXCL10) decreased. Pexelizumab halved the increase in IL-6 (+ 92% vs 156%, P = .01) without effects on other markers, including C-reactive protein and N-terminal probrain natriuretic peptide. In cell culture, pexelizumab inhibited C5a, sC5b-9, and membrane-bound C5b-9 by 92%, 75%, and 78%, respectively (all P < .0001), without influencing cytokine levels and cell apoptosis. Conclusions The blockage of both C5a and terminal complement in cell culture, but of C5a only in vivo with minimal effects on inflammation and risk biomarkers, supports the hypothesis that late administration of pexelizumab after the ischemia/reperfusion insult precluded adequate myocardial protection, resulting in a negative trial.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0002-8703
fulltext: fulltext
issn:
  • 0002-8703
  • 1097-6744
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.458304
LOCALfalse
PrimoNMBib
record
control
sourceidgale_proqu
recordidTN_cdi_proquest_miscellaneous_1026695837
sourceformatXML
sourcesystemPC
galeidA296326347
sourcerecordidA296326347
originalsourceidFETCH-LOGICAL-c523t-1d11bde78cfa8be1c2439b35c1a33dd0a5bdb2a6202b2b6098b7abe9a8e1f94f3
addsrcrecordideNp9U11rFDEUHUWxa_UHCCIBEerDrEnmG0FYStWFFgut4FvIZO7sZp1J1iRTu_5673TXrhYp8zDJnXNOztx7EkUvGJ0yyvJ3q6lcrqacMj6l6ZTS4mE0YbQq4rxI00fRhFLK47KgyUH01PsVbnNe5k-iA86LKuMlmzx4eQ7X0OlfQy9r0krdeRIs0Wapax2I9B76utsQ25KwBBLA9drIjijbrzvowYTd8ho5ZC2DxpInP3VYkovLGDq4wpo1pN9YJV2jkatNK526qQ6mAbew2izI2uleug1Zg1NDkAbs4FHbWTNWtcGjr1AbWVMyN14vloG0zvZEEj_UPgzNrcsZuvb-xhxW_v5B9DhDdSBnezvzvZ2j2fnJt3h2Nn9LgsNvz6LHrew8PN-9D6OvH08ujz_Hp18-zY9np7HKeBJi1jBWN1CUqpVlDUzxNKnqJFNMJknTUJnVTc1lzimveZ3TqqwLWUMlS2BtlbbJYXS01V07-2MAH0SvvYKu27ZBMMrzvMrKpEDo6zvQlR0cjgRRGU3zpEwzukctZAcCG26Dk2oUFTNe5QnPk3TUmv4HhU8DvVbWQKux_g-BbQnKWe8dtGI3NXQoxkSKlcBEijGRgqYCE4mcVzvDQ91Dc8v4E0EEvNkBpFeya500Svs9LmdlRlmJuOLO4UqHm3Cha93da-H9lgk4wysNTniFOVXQaAcqiMbqe9kf7rBVp41Gq99hA37ffuGRIy7GSzfeOcZxUaHx37LsKwM
sourcetypeAggregation Database
isCDItrue
recordtypearticle
pqid1504638450
display
typearticle
titlePexelizumab fails to inhibit assembly of the terminal complement complex in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Insight from a substudy of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial
sourceAlma/SFX Local Collection
creatorMartel, Catherine, PhD ; Granger, Christopher B., MD ; Ghitescu, Marta, MS ; Stebbins, Amanda, MS ; Fortier, Annik, MS ; Armstrong, Paul W., MD ; Bonnefoy, Arnaud, PhD ; Theroux, Pierre, MD
creatorcontribMartel, Catherine, PhD ; Granger, Christopher B., MD ; Ghitescu, Marta, MS ; Stebbins, Amanda, MS ; Fortier, Annik, MS ; Armstrong, Paul W., MD ; Bonnefoy, Arnaud, PhD ; Theroux, Pierre, MD
descriptionBackground Reasons for pexelizumab lack of benefit in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention remain unclear. In a substudy of the APEX-AMI trial, we explored the hypothesis that early complement activation preceding drug administration explained the failure. Methods A panel of terminal complement complex proteins and fragments and biomarkers of inflammation, apoptosis, and high-risk features were assessed in serum obtained before and 24 hours after administration of placebo or pexelizumab and primary percutaneous coronary intervention (n = 356) and in human umbilical vein endothelial cell cultures coincubated with serum (n = 45). Results In the placebo group, C5a and sC5b-9 levels increased by 37% (7.9-14.2 ηg/mL, P = .007) and 96% (442-845 ηg/mL, P < .0001), respectively, during the first 24 hours. Pexelizumab prevented the increase in C5a ( P = .01 vs placebo), but not that of sC5b-9 (502-1,157 ηg/mL, not significant vs placebo). Levels of C-reactive protein, interleukin (IL) 6, IL-1ß, Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) or Chemokine C-C motif ligand 5 (CCL5), and N-terminal probrain natriuretic peptide increased significantly in both groups; those of IL-10, IL-12, IL-1ra, and Interferon gamma-induced protein 10 (IP-10) or C-X-C motif chemokine 10 (CXCL10) decreased. Pexelizumab halved the increase in IL-6 (+ 92% vs 156%, P = .01) without effects on other markers, including C-reactive protein and N-terminal probrain natriuretic peptide. In cell culture, pexelizumab inhibited C5a, sC5b-9, and membrane-bound C5b-9 by 92%, 75%, and 78%, respectively (all P < .0001), without influencing cytokine levels and cell apoptosis. Conclusions The blockage of both C5a and terminal complement in cell culture, but of C5a only in vivo with minimal effects on inflammation and risk biomarkers, supports the hypothesis that late administration of pexelizumab after the ischemia/reperfusion insult precluded adequate myocardial protection, resulting in a negative trial.
identifier
0ISSN: 0002-8703
1EISSN: 1097-6744
2DOI: 10.1016/j.ahj.2012.04.007
3PMID: 22795281
4CODEN: AHJOA2
languageeng
publisherNew York, NY: Mosby, Inc
subjectAbridged Index Medicus ; Aged ; Analysis ; Angioplasty, Balloon, Coronary ; Antibodies, Monoclonal, Humanized - therapeutic use ; Apoptosis ; Biological and medical sciences ; Cardiac patients ; Cardiology. Vascular system ; Cardiovascular ; Care and treatment ; Cell culture ; Complement Membrane Attack Complex - antagonists & inhibitors ; Coronary heart disease ; Diseases of the cardiovascular system ; Double-Blind Method ; Female ; Heart ; Heart attack ; Heart attacks ; Humans ; Male ; Medical sciences ; Middle Aged ; Mortality ; Myocardial Infarction - therapy ; Myocarditis. Cardiomyopathies ; Prospective Studies ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; Single-Chain Antibodies - therapeutic use ; Transluminal angioplasty ; Treatment Failure
ispartofThe American heart journal, 2012, Vol.164 (1), p.43-51
rights
0Mosby, Inc.
12012 Mosby, Inc.
22015 INIST-CNRS
3Copyright © 2012 Mosby, Inc. All rights reserved.
4COPYRIGHT 2012 Elsevier B.V.
5Copyright Elsevier Limited Jul 2012
lds50peer_reviewed
citedbyFETCH-LOGICAL-c523t-1d11bde78cfa8be1c2439b35c1a33dd0a5bdb2a6202b2b6098b7abe9a8e1f94f3
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
thumbnail$$Usyndetics_thumb_exl
backlink
0$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26185018$$DView record in Pascal Francis
1$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22795281$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0Martel, Catherine, PhD
1Granger, Christopher B., MD
2Ghitescu, Marta, MS
3Stebbins, Amanda, MS
4Fortier, Annik, MS
5Armstrong, Paul W., MD
6Bonnefoy, Arnaud, PhD
7Theroux, Pierre, MD
title
0Pexelizumab fails to inhibit assembly of the terminal complement complex in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Insight from a substudy of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial
1The American heart journal
addtitleAm Heart J
descriptionBackground Reasons for pexelizumab lack of benefit in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention remain unclear. In a substudy of the APEX-AMI trial, we explored the hypothesis that early complement activation preceding drug administration explained the failure. Methods A panel of terminal complement complex proteins and fragments and biomarkers of inflammation, apoptosis, and high-risk features were assessed in serum obtained before and 24 hours after administration of placebo or pexelizumab and primary percutaneous coronary intervention (n = 356) and in human umbilical vein endothelial cell cultures coincubated with serum (n = 45). Results In the placebo group, C5a and sC5b-9 levels increased by 37% (7.9-14.2 ηg/mL, P = .007) and 96% (442-845 ηg/mL, P < .0001), respectively, during the first 24 hours. Pexelizumab prevented the increase in C5a ( P = .01 vs placebo), but not that of sC5b-9 (502-1,157 ηg/mL, not significant vs placebo). Levels of C-reactive protein, interleukin (IL) 6, IL-1ß, Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) or Chemokine C-C motif ligand 5 (CCL5), and N-terminal probrain natriuretic peptide increased significantly in both groups; those of IL-10, IL-12, IL-1ra, and Interferon gamma-induced protein 10 (IP-10) or C-X-C motif chemokine 10 (CXCL10) decreased. Pexelizumab halved the increase in IL-6 (+ 92% vs 156%, P = .01) without effects on other markers, including C-reactive protein and N-terminal probrain natriuretic peptide. In cell culture, pexelizumab inhibited C5a, sC5b-9, and membrane-bound C5b-9 by 92%, 75%, and 78%, respectively (all P < .0001), without influencing cytokine levels and cell apoptosis. Conclusions The blockage of both C5a and terminal complement in cell culture, but of C5a only in vivo with minimal effects on inflammation and risk biomarkers, supports the hypothesis that late administration of pexelizumab after the ischemia/reperfusion insult precluded adequate myocardial protection, resulting in a negative trial.
subject
0Abridged Index Medicus
1Aged
2Analysis
3Angioplasty, Balloon, Coronary
4Antibodies, Monoclonal, Humanized - therapeutic use
5Apoptosis
6Biological and medical sciences
7Cardiac patients
8Cardiology. Vascular system
9Cardiovascular
10Care and treatment
11Cell culture
12Complement Membrane Attack Complex - antagonists & inhibitors
13Coronary heart disease
14Diseases of the cardiovascular system
15Double-Blind Method
16Female
17Heart
18Heart attack
19Heart attacks
20Humans
21Male
22Medical sciences
23Middle Aged
24Mortality
25Myocardial Infarction - therapy
26Myocarditis. Cardiomyopathies
27Prospective Studies
28Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
29Single-Chain Antibodies - therapeutic use
30Transluminal angioplasty
31Treatment Failure
issn
00002-8703
11097-6744
fulltexttrue
rsrctypearticle
creationdate2012
recordtypearticle
recordideNp9U11rFDEUHUWxa_UHCCIBEerDrEnmG0FYStWFFgut4FvIZO7sZp1J1iRTu_5673TXrhYp8zDJnXNOztx7EkUvGJ0yyvJ3q6lcrqacMj6l6ZTS4mE0YbQq4rxI00fRhFLK47KgyUH01PsVbnNe5k-iA86LKuMlmzx4eQ7X0OlfQy9r0krdeRIs0Wapax2I9B76utsQ25KwBBLA9drIjijbrzvowYTd8ho5ZC2DxpInP3VYkovLGDq4wpo1pN9YJV2jkatNK526qQ6mAbew2izI2uleug1Zg1NDkAbs4FHbWTNWtcGjr1AbWVMyN14vloG0zvZEEj_UPgzNrcsZuvb-xhxW_v5B9DhDdSBnezvzvZ2j2fnJt3h2Nn9LgsNvz6LHrew8PN-9D6OvH08ujz_Hp18-zY9np7HKeBJi1jBWN1CUqpVlDUzxNKnqJFNMJknTUJnVTc1lzimveZ3TqqwLWUMlS2BtlbbJYXS01V07-2MAH0SvvYKu27ZBMMrzvMrKpEDo6zvQlR0cjgRRGU3zpEwzukctZAcCG26Dk2oUFTNe5QnPk3TUmv4HhU8DvVbWQKux_g-BbQnKWe8dtGI3NXQoxkSKlcBEijGRgqYCE4mcVzvDQ91Dc8v4E0EEvNkBpFeya500Svs9LmdlRlmJuOLO4UqHm3Cha93da-H9lgk4wysNTniFOVXQaAcqiMbqe9kf7rBVp41Gq99hA37ffuGRIy7GSzfeOcZxUaHx37LsKwM
startdate2012
enddate2012
creator
0Martel, Catherine, PhD
1Granger, Christopher B., MD
2Ghitescu, Marta, MS
3Stebbins, Amanda, MS
4Fortier, Annik, MS
5Armstrong, Paul W., MD
6Bonnefoy, Arnaud, PhD
7Theroux, Pierre, MD
general
0Mosby, Inc
1Mosby
2Elsevier B.V
3Elsevier Limited
scope
0IQODW
1CGR
2CUY
3CVF
4ECM
5EIF
6NPM
7AAYXX
8CITATION
9BSHEE
103V.
117QO
127RV
137TS
147X7
157XB
1688C
1788E
188AO
198C1
208FD
218FI
228FJ
238FK
248G5
25ABUWG
26AN0
27AZQEC
28BENPR
29DWQXO
30FR3
31FYUFA
32GHDGH
33GNUQQ
34GUQSH
35K9.
36KB0
37M0S
38M0T
39M1P
40M2O
41MBDVC
42NAPCQ
43P64
44PADUT
45PQEST
46PQQKQ
47PQUKI
48PRINS
49Q9U
507X8
sort
creationdate2012
titlePexelizumab fails to inhibit assembly of the terminal complement complex in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Insight from a substudy of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial
authorMartel, Catherine, PhD ; Granger, Christopher B., MD ; Ghitescu, Marta, MS ; Stebbins, Amanda, MS ; Fortier, Annik, MS ; Armstrong, Paul W., MD ; Bonnefoy, Arnaud, PhD ; Theroux, Pierre, MD
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-c523t-1d11bde78cfa8be1c2439b35c1a33dd0a5bdb2a6202b2b6098b7abe9a8e1f94f3
rsrctypearticles
prefilterarticles
languageeng
creationdate2012
topic
0Abridged Index Medicus
1Aged
2Analysis
3Angioplasty, Balloon, Coronary
4Antibodies, Monoclonal, Humanized - therapeutic use
5Apoptosis
6Biological and medical sciences
7Cardiac patients
8Cardiology. Vascular system
9Cardiovascular
10Care and treatment
11Cell culture
12Complement Membrane Attack Complex - antagonists & inhibitors
13Coronary heart disease
14Diseases of the cardiovascular system
15Double-Blind Method
16Female
17Heart
18Heart attack
19Heart attacks
20Humans
21Male
22Medical sciences
23Middle Aged
24Mortality
25Myocardial Infarction - therapy
26Myocarditis. Cardiomyopathies
27Prospective Studies
28Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
29Single-Chain Antibodies - therapeutic use
30Transluminal angioplasty
31Treatment Failure
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Martel, Catherine, PhD
1Granger, Christopher B., MD
2Ghitescu, Marta, MS
3Stebbins, Amanda, MS
4Fortier, Annik, MS
5Armstrong, Paul W., MD
6Bonnefoy, Arnaud, PhD
7Theroux, Pierre, MD
collection
0Pascal-Francis
1Medline
2MEDLINE
3MEDLINE (Ovid)
4MEDLINE
5MEDLINE
6PubMed
7CrossRef
8Academic OneFile (A&I only)
9ProQuest Central (Corporate)
10Biotechnology Research Abstracts
11Nursing & Allied Health Database
12Physical Education Index
13Health & Medical Collection
14ProQuest Central (purchase pre-March 2016)
15Healthcare Administration Database (Alumni)
16Medical Database (Alumni Edition)
17ProQuest Pharma Collection
18Public Health Database
19Technology Research Database
20Hospital Premium Collection
21Hospital Premium Collection (Alumni Edition)
22ProQuest Central (Alumni) (purchase pre-March 2016)
23Research Library (Alumni Edition)
24ProQuest Central (Alumni Edition)
25British Nursing Database
26ProQuest Central Essentials
27ProQuest Central
28ProQuest Central Korea
29Engineering Research Database
30Health Research Premium Collection
31Health Research Premium Collection (Alumni)
32ProQuest Central Student
33Research Library Prep
34ProQuest Health & Medical Complete (Alumni)
35Nursing & Allied Health Database (Alumni Edition)
36Health & Medical Collection (Alumni Edition)
37Healthcare Administration Database
38Medical Database
39Research Library
40Research Library (Corporate)
41Nursing & Allied Health Premium
42Biotechnology and BioEngineering Abstracts
43Research Library China
44ProQuest One Academic Eastern Edition
45ProQuest One Academic
46ProQuest One Academic UKI Edition
47ProQuest Central China
48ProQuest Central Basic
49MEDLINE - Academic
jtitleThe American heart journal
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Martel, Catherine, PhD
1Granger, Christopher B., MD
2Ghitescu, Marta, MS
3Stebbins, Amanda, MS
4Fortier, Annik, MS
5Armstrong, Paul W., MD
6Bonnefoy, Arnaud, PhD
7Theroux, Pierre, MD
formatjournal
genrearticle
ristypeJOUR
atitlePexelizumab fails to inhibit assembly of the terminal complement complex in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Insight from a substudy of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial
jtitleThe American heart journal
addtitleAm Heart J
date2012
risdate2012
volume164
issue1
spage43
epage51
pages43-51
issn0002-8703
eissn1097-6744
codenAHJOA2
abstractBackground Reasons for pexelizumab lack of benefit in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention remain unclear. In a substudy of the APEX-AMI trial, we explored the hypothesis that early complement activation preceding drug administration explained the failure. Methods A panel of terminal complement complex proteins and fragments and biomarkers of inflammation, apoptosis, and high-risk features were assessed in serum obtained before and 24 hours after administration of placebo or pexelizumab and primary percutaneous coronary intervention (n = 356) and in human umbilical vein endothelial cell cultures coincubated with serum (n = 45). Results In the placebo group, C5a and sC5b-9 levels increased by 37% (7.9-14.2 ηg/mL, P = .007) and 96% (442-845 ηg/mL, P < .0001), respectively, during the first 24 hours. Pexelizumab prevented the increase in C5a ( P = .01 vs placebo), but not that of sC5b-9 (502-1,157 ηg/mL, not significant vs placebo). Levels of C-reactive protein, interleukin (IL) 6, IL-1ß, Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) or Chemokine C-C motif ligand 5 (CCL5), and N-terminal probrain natriuretic peptide increased significantly in both groups; those of IL-10, IL-12, IL-1ra, and Interferon gamma-induced protein 10 (IP-10) or C-X-C motif chemokine 10 (CXCL10) decreased. Pexelizumab halved the increase in IL-6 (+ 92% vs 156%, P = .01) without effects on other markers, including C-reactive protein and N-terminal probrain natriuretic peptide. In cell culture, pexelizumab inhibited C5a, sC5b-9, and membrane-bound C5b-9 by 92%, 75%, and 78%, respectively (all P < .0001), without influencing cytokine levels and cell apoptosis. Conclusions The blockage of both C5a and terminal complement in cell culture, but of C5a only in vivo with minimal effects on inflammation and risk biomarkers, supports the hypothesis that late administration of pexelizumab after the ischemia/reperfusion insult precluded adequate myocardial protection, resulting in a negative trial.
copNew York, NY
pubMosby, Inc
pmid22795281
doi10.1016/j.ahj.2012.04.007