Hemodynamic effects of bradykinin antagonism in porcine gram-negative sepsis
Activation of the kallikrein-kinin system in sepsis has long been recognized, but its role, beneficial or pathologic, has not been defined. Recently, however, specific bradykinin (BK) antagonists have become available and this study investigated the effects of a BK antagonist, NPC17731 (Scios-Nova)...
Saved in:
Published in | Journal of investigative surgery Vol. 8; no. 2; p. 115 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
1995
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | Activation of the kallikrein-kinin system in sepsis has long been recognized, but its role, beneficial or pathologic, has not been defined. Recently, however, specific bradykinin (BK) antagonists have become available and this study investigated the effects of a BK antagonist, NPC17731 (Scios-Nova) on systemic and pulmonary hemodynamics in a model of gram-negative sepsis. Anesthetized swine were studied for 5 h receiving a 1-h infusion of saline (controls, group 1, N = 8) or live Pseudomonas aeruginosa (septic, group 2, N = 8). Group 3 (treatment, N = 6) received NPC17731 (5 mg/kg initial bolus followed by 1 mg/kg hourly) just prior to the onset of sepsis. Group 2 animals showed a rapid decrease in systemic arterial pressure (SAP) from 30 min onward, and sustained significant hypotension from 2 h onward. In group 3, SAP fell similarly until 2 h then progressively rose, returning to baseline levels by 5 h. In contrast, cardiac index fell progressively from 3 h onward in groups 2 and 3. Systemic vascular resistance index (SVRI) fell significantly by 2 h in group 2 animals, recovering to baseline by 5 h. Group 3 showed a similar initial fall followed by a rebound increase in SVRI, which, at 5 h was significantly raised above the other groups. Group 2 developed significant, persistent pulmonary artery hypertension which was not reduced by NPC17731. The data imply a significant role for bradykinin in the pathogenesis of hypotension in septic shock in this model. Septic shock was reversed by a BK antagonist which increased peripheral resistance without affecting cardiac output. |
---|---|
AbstractList | Activation of the kallikrein-kinin system in sepsis has long been recognized, but its role, beneficial or pathologic, has not been defined. Recently, however, specific bradykinin (BK) antagonists have become available and this study investigated the effects of a BK antagonist, NPC17731 (Scios-Nova) on systemic and pulmonary hemodynamics in a model of gram-negative sepsis. Anesthetized swine were studied for 5 h receiving a 1-h infusion of saline (controls, group 1, N = 8) or live Pseudomonas aeruginosa (septic, group 2, N = 8). Group 3 (treatment, N = 6) received NPC17731 (5 mg/kg initial bolus followed by 1 mg/kg hourly) just prior to the onset of sepsis. Group 2 animals showed a rapid decrease in systemic arterial pressure (SAP) from 30 min onward, and sustained significant hypotension from 2 h onward. In group 3, SAP fell similarly until 2 h then progressively rose, returning to baseline levels by 5 h. In contrast, cardiac index fell progressively from 3 h onward in groups 2 and 3. Systemic vascular resistance index (SVRI) fell significantly by 2 h in group 2 animals, recovering to baseline by 5 h. Group 3 showed a similar initial fall followed by a rebound increase in SVRI, which, at 5 h was significantly raised above the other groups. Group 2 developed significant, persistent pulmonary artery hypertension which was not reduced by NPC17731. The data imply a significant role for bradykinin in the pathogenesis of hypotension in septic shock in this model. Septic shock was reversed by a BK antagonist which increased peripheral resistance without affecting cardiac output. |
Author | Blocher, C R Sugerman, H J Fisher, B J Ridings, P C Fowler, A A |
Author_xml | – sequence: 1 givenname: P C surname: Ridings fullname: Ridings, P C organization: Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA – sequence: 2 givenname: H J surname: Sugerman fullname: Sugerman, H J – sequence: 3 givenname: C R surname: Blocher fullname: Blocher, C R – sequence: 4 givenname: B J surname: Fisher fullname: Fisher, B J – sequence: 5 givenname: A A surname: Fowler fullname: Fowler, A A |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/7619781$$D View this record in MEDLINE/PubMed |
BookMark | eNotj81KxDAURrMYGWdGH8CFkBeo5j-9SxnUEQpudD2k6U2JmrQ0Vejb6-CsDt9ZfHC2ZJWHjITccHYnOYN7VoPiIEEzYNxorlZkc3LVSV6SbSkfjDGhQK7J2hoOtuYb0hwwDd2SXYqeYgjo50KHQNvJdctnzDFTl2fXDzmWRP_WOEw-ZqT95FKVsXdz_EFacCyxXJGL4L4KXp-5I-9Pj2_7Q9W8Pr_sH5rKK8bnygQt0UgAlEF7tE5p5xSEVoESUgopamWCxSCZtboFb4zxvDVWSN5pI8SO3P7_jt9twu44TjG5aTmeq8QvS3tO3w |
CitedBy_id | crossref_primary_10_1111_bph_14685 crossref_primary_10_1038_ki_2008_647 crossref_primary_10_1186_s40560_017_0228_x crossref_primary_10_1186_s40635_019_0228_3 crossref_primary_10_1016_0162_3109_96_00060_4 crossref_primary_10_1016_S1045_1870_99_80044_2 crossref_primary_10_3390_ph13090215 crossref_primary_10_3389_fmed_2016_00052 crossref_primary_10_1517_17460441_2012_729038 |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM |
DOI | 10.3109/08941939509016514 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
ExternalDocumentID | 7619781 |
Genre | Research Support, U.S. Gov't, Non-P.H.S Journal Article |
GroupedDBID | --- .4L .GJ 00X 03L 0BK 0YH 29K 34G 36B 39C 4.4 53G 5GY 5RE 5VS AALIY AALUX AAMIU AAORF AAPUL AAPXX AAQRR ABBKH ABDBF ABEIZ ABJNI ABLIJ ABLKL ABUPF ABWCV ABXYU ABZEW ACENM ACGEJ ACGFS ACKZS ACLSK ADCVX ADFOM ADFZZ ADRBQ ADXPE AECIN AEIIZ AENEX AEOZL AFKVX AFLEI AFWLO AGDLA AGFJD AGRBW AGYJP AIJEM AJVHN AJWEG AKBVH ALMA_UNASSIGNED_HOLDINGS ALQZU ALYBC AMDAE AWYRJ B0M BABNJ BLEHA BOHLJ BRMBE CAG CCCUG CGR COF CS3 CUY CVF CYYVM CZDIS D-I DKSSO DRXRE DU5 DWTOO EAP EAS EBB EBC EBD EBS EBX ECM EHL EHN EIF EJD EMB EMK EMOBN EPL EPT EST ESX F5P GROUPED_DOAJ H13 HZ~ JENTW KRBQP KSSTO KWAYT KYCEM LJTGL NPM NUSFT O9- P2P QQXMO Q~Q RNANH RVRKI SV3 TBQAZ TDBHL TERGH TFDNU TFL TFW TUROJ TUS UEQFS V1S ZGI ~1N |
ID | FETCH-LOGICAL-c401t-6f53e6399e3f5ce7a45aa49fb494233232846f7ef30775b9c666c1b67231d5622 |
ISSN | 0894-1939 |
IngestDate | Sat Sep 28 08:35:01 EDT 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 2 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c401t-6f53e6399e3f5ce7a45aa49fb494233232846f7ef30775b9c666c1b67231d5622 |
PMID | 7619781 |
ParticipantIDs | pubmed_primary_7619781 |
PublicationCentury | 1900 |
PublicationDate | 1995-00-00 |
PublicationDateYYYYMMDD | 1995-01-01 |
PublicationDate_xml | – year: 1995 text: 1995-00-00 |
PublicationDecade | 1990 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Journal of investigative surgery |
PublicationTitleAlternate | J Invest Surg |
PublicationYear | 1995 |
SSID | ssj0002493 |
Score | 1.4453506 |
Snippet | Activation of the kallikrein-kinin system in sepsis has long been recognized, but its role, beneficial or pathologic, has not been defined. Recently, however,... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | 115 |
SubjectTerms | Animals Bradykinin - antagonists & inhibitors Gram-Negative Bacterial Infections - physiopathology Hemodynamics - drug effects Oligopeptides - pharmacology Sepsis - microbiology Sepsis - physiopathology Swine |
Title | Hemodynamic effects of bradykinin antagonism in porcine gram-negative sepsis |
URI | https://www.ncbi.nlm.nih.gov/pubmed/7619781 |
Volume | 8 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LS8NAEF6sIvQiihbf7MFbidrs5nW0ogTRnlroreSxW4o2KaYe9Nc7s7s1a7WiXkKSDUuS-TL5ZudFyBlWqeKZ5A4LXTBQAj93UsaYA8ZzyMIkyH3VveGh58cDfjf0hrUrRmWXzNPz7O3bvJL_SBXOgVwxS_YPkv2YFE7APsgXtiBh2P5KxrGYlrluKW8HZoABnL8-YueHNry3ZAyfbTVV4eLlM_rR2xiR5RRirIt-V2JWTaoVLHVS1-HAS60kalX5WnmuFBO1lltfxqjulTqLa7dT96lcAMQKU6xbr3fNpbnJyfOsJQijqSLuABOMbLUaWuhxLRXZ0emby6qb6cqnOBXOBDwGE610gqklytlUyRIXXwLd6-XHwaVa2makQRpBiOqwh0s75rcNdqgKR1g8i3aB421dfLmpJtk0Uy1ZI4qV9LfJlhEUvdLY2CFrotgl9xYuqMEFLSWtcUFrXFA4Mrign3BBNS72yOD2pn8dO6ZrhpOBrTx3fOkxgbxTMOllIki4lyQ8kimPgDozYNBAOWUgJMPqh2mUgQGbdVI_AKafAxt2W2S9KAuxTyhQZ7A_JXe5CLjMvRT_BpcdwX0Xaz5FB6SlH34006VRRuatHK4aOCLNGkDHZEPClyhOgNbN01MljnfRYEg4 |
link.rule.ids | 786 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Hemodynamic+effects+of+bradykinin+antagonism+in+porcine+gram-negative+sepsis&rft.jtitle=Journal+of+investigative+surgery&rft.au=Ridings%2C+P+C&rft.au=Sugerman%2C+H+J&rft.au=Blocher%2C+C+R&rft.au=Fisher%2C+B+J&rft.date=1995-01-01&rft.issn=0894-1939&rft.volume=8&rft.issue=2&rft.spage=115&rft_id=info:doi/10.3109%2F08941939509016514&rft_id=info%3Apmid%2F7619781&rft_id=info%3Apmid%2F7619781&rft.externalDocID=7619781 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0894-1939&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0894-1939&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0894-1939&client=summon |