• SyncroPatch 384

    Next level versatility and flexibility
  • SyncroPatch 384

    True HTS and GigaOhm seals
  • SyncroPatch 384

    Your multi purpose instrument
  • SyncroPatch 384

    Powerful analysis software
  • SyncroPatch 384

    Assay flexibility via high tech
  • SyncroPatch 384

    Heating and cooling of solutions, cells and patch clamp sites

2021 - Cardiovascular and Respiratory Toxicity of Protamine Sulfate in Zebrafish and Rodent Models

icon sp96  SyncroPatch 384PE (a predecessor model of the SyncroPatch 384 instrument) Publication in Pharmaceutics (2021)

Authors:
Miklosz J., Kalaska B., Podlasz P., Chmielewska-Krzesińska M., Zajączkowski M., Kosiński A., Pawlak D., Mogielnicki A.

Journal:

Pharmaceutics (2021) doi:10.3390/pharmaceutics13030359


Abstract: 

Protamine sulfate (PS) is the only available option to reverse the anticoagulant activity of unfractionated heparin (UFH), however it can cause cardiovascular and respiratory complications. We explored the toxicity of PS and its complexes with UFH in zebrafish, rats, and mice. The involvement of nitric oxide (NO) in the above effects was investigated. Concentration–dependent lethality, morphological defects, and decrease in heart rate (HR) were observed in zebrafish larvae. PS affected HR, blood pressure, respiratory rate, peak exhaled CO2, and blood oxygen saturation in rats. We observed hypotension, increase of HR, perfusion of paw vessels, and enhanced respiratory disturbances with increases doses of PS. We found no effects of PS on human hERG channels or signs of heart damage in mice. The hypotension in rats and bradycardia in zebrafish were partially attenuated by the inhibitor of endothelial NO synthase. The disturbances in cardiovascular and respiratory parameters were reduced or delayed when PS was administered together with UFH. The cardiorespiratory toxicity of PS seems to be charge–dependent and involves enhanced release of NO. PS administered at appropriate doses and ratios with UFH should not cause permanent damage of heart tissue, although careful monitoring of cardiorespiratory parameters is necessary.


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