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Related Experiment Videos

Protamine cardiotoxicity and nitric oxide.

D Pevni1, I Frolkis, A Iaina

  • 1Department of Cardiothoracic Surgery, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel. shapiraiz@tasmc.health.gov.il

European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery
|June 26, 2001
PubMed
Summary
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Protamine cardiotoxicity in isolated rat hearts does not involve the nitric oxide (NO) pathway. Instead, protamine induces tumor necrosis factor-alpha (TNF) release from cardiomyocytes, offering a new perspective on its adverse effects.

Area of Science:

  • Cardiovascular Physiology
  • Pharmacology
  • Molecular Biology

Background:

  • Protamine is used to reverse heparin anticoagulation but can cause cardiotoxicity.
  • The underlying mechanisms of protamine-induced cardiotoxicity are not fully understood.
  • The role of the nitric oxide (NO) pathway in this adverse effect requires investigation.

Purpose of the Study:

  • To evaluate the involvement of the nitric oxide (NO) pathway in protamine-induced cardiotoxicity.
  • To explore potential mechanisms behind protamine's adverse cardiac effects.

Main Methods:

  • Isolated rat hearts were perfused using a Langendorff model.
  • Hearts were exposed to Krebs-Henseleit solution, protamine, or protamine with L-NMMA (a NO pathway inhibitor).
  • Left ventricular function, nitric oxide (NO), and tumor necrosis factor-alpha (TNF) levels were measured.

Related Experiment Videos

Main Results:

  • Protamine significantly depressed left ventricular function.
  • L-NMMA did not mitigate protamine-induced cardiotoxicity.
  • Protamine induced significant release of TNF from cardiomyocytes, while NO levels remained undetectable.

Conclusions:

  • Direct protamine cardiotoxicity is independent of the nitric oxide (NO) pathway.
  • Protamine-induced TNF release by cardiomyocytes is a key factor in its cardiotoxicity.
  • This finding provides novel insights into the mechanisms of protamine's adverse cardiac effects.