Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
OtherCARDIOVASCULAR PHARMACOLOGY

The Semisynthetic Polysaccharide Pentosan Polysulfate Prevents Complement-Mediated Myocardial Injury in the Rabbit Perfused Heart

Kenneth S. Kilgore, Keith B. Naylor, Elaine J. Tanhehco, James L. Park, Erin A. Booth, Ruth A. Washington and Benedict R. Lucchesi
Journal of Pharmacology and Experimental Therapeutics June 1998, 285 (3) 987-994;
Kenneth S. Kilgore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keith B. Naylor
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elaine J. Tanhehco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James L. Park
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erin A. Booth
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ruth A. Washington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benedict R. Lucchesi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Pentosan polysulfate (PPS) is a highly sulfated semisynthetic polysaccharide possessing a higher negative charge density and degree of sulfation than heparin. Like other glycosaminoglycans, the structural and chemical properties of PPS promote binding of the drug to the endothelium. Glycosaminoglycans, including heparin, inhibit complement activation independent of an action on the coagulation system. This ability provides a compelling argument for the implementation of this class of compounds in experimental models of cellular injury mediated by complement. The objective of this study was to examine whether PPS could reduce myocardial injury resulting from activation of the complement system. We used the rabbit isolated heart perfused with 4% normal human plasma as a source of complement. Hemodynamic variables were obtained before addition of PPS (0.03 01 mg/ml) and every 10 min after the addition of human plasma. Compared with vehicle-treated hearts, left ventricular end-diastolic pressure was improved at the conclusion of the 60-min protocol in hearts treated with PPS (58.9 ± 13.6 vs. 15.2 ± 4.8 mm Hg). Further evidence as to the protective effects of PPS was demonstrated by decreased creatine kinase release compared with vehicle (86.5 ± 28.5 U/l vs. 631.0 ± 124.8 U/l). An enzyme-linked immunosorbent assay for the presence of the membrane attack complex in lymph and tissue samples demonstrated decreased membrane attack complex formation in PPS-treated hearts, which suggests inhibition of complement activation. This conclusion was supported further by the ability of PPS to inhibit complement-mediated red blood cell lysis in vitro. The results of this study indicate that PPS can reduce tissue injury and preserve organ function that otherwise would be compromised during activation of the human complement cascade.

Footnotes

  • Send reprint requests to: Kenneth S. Kilgore, Ph.D., Department of Pharmacology, University of Michigan Medical School, 1301C Medical Science Research Building III, Ann Arbor, MI 48109-0632.

  • ↵1 This study was funded by the Cardiovascular Research Fund, University of Michigan Medical School, Department of Pharmacology. KSK was supported, in part, by the American Heart Association, Michigan Affiliate (no. 36GB967).

  • ↵2 Awarded a summer research student fellowship from the American Heart Association, Michigan Affiliate, during the tenure of this study.

  • Abbreviations:
    PPS
    pentosan polysulfate
    MAC
    membrane attack complex
    GAG
    glycosaminoglycans
    NHP
    normal human plasma
    GVB
    gelatin veronal buffer
    CK
    creatine kinase
    LVEDP
    left ventricular end-diastolic pressure
    LVDP
    left ventricular developed pressure
    RBC
    red blood cell
    EGTA
    ethyleneglycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid
    ELISA
    enzyme-linked immunosorbent assay
    • Received July 21, 1997.
    • Accepted February 16, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 3
1 Jun 1998
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
The Semisynthetic Polysaccharide Pentosan Polysulfate Prevents Complement-Mediated Myocardial Injury in the Rabbit Perfused Heart
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherCARDIOVASCULAR PHARMACOLOGY

The Semisynthetic Polysaccharide Pentosan Polysulfate Prevents Complement-Mediated Myocardial Injury in the Rabbit Perfused Heart

Kenneth S. Kilgore, Keith B. Naylor, Elaine J. Tanhehco, James L. Park, Erin A. Booth, Ruth A. Washington and Benedict R. Lucchesi
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 987-994;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
OtherCARDIOVASCULAR PHARMACOLOGY

The Semisynthetic Polysaccharide Pentosan Polysulfate Prevents Complement-Mediated Myocardial Injury in the Rabbit Perfused Heart

Kenneth S. Kilgore, Keith B. Naylor, Elaine J. Tanhehco, James L. Park, Erin A. Booth, Ruth A. Washington and Benedict R. Lucchesi
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 987-994;
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Preconditioning of Rat Heart with Monophosphoryl Lipid A: A Role for Nitric Oxide
  • TAS-301, an Inhibitor of Smooth Muscle Cell Migration and Proliferation, Inhibits Intimal Thickening after Balloon Injury to Rat Carotid Arteries
  • Identification of Low Molecular Weight GP IIb/IIIa Antagonists That Bind Preferentially to Activated Platelets
Show more CARDIOVASCULAR PHARMACOLOGY

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics