Alteplase and DNase for the treatment of pleural empyema in rats

Pulm Pharmacol Ther. 2019 Apr:55:1-4. doi: 10.1016/j.pupt.2019.01.001. Epub 2019 Jan 14.

Abstract

Background and objectives: Adjunctive intrapleural fibrinolytic is an option to treat empyema at fibrinopurulent stage, but there is controversy about which should be use. Our objective is to evaluate the action of alteplase and/or desoxyribonuclease at physical and chemical properties in vitro pus derived from an experimental induced empyema in rats.

Methods: Streptococcus pneumoniae was introduced into the pleural cavity by thoracentesis through pleural pressure monitor. Animals were euthanized after 24 h, with macroscopic thoracic evaluation and measurement of amount of intrapleural liquid that was posteriorly stored at -80 °C. Selected samples were randomly distributed into four groups, then thawed at room temperature before exposure to one of the following: G1 = alteplase (n = 12), G2 = DNase (n = 12), G3 = alteplase + DNase (n = 12), or G4 = saline (n = 6). The mean molecular size in the fluid portion of the empyema was evaluated using dynamic light scattering; viscosity of the empyema fluid was measured using the drip method.

Results: Macroscopic showed purulent liquid, with fibrin and septation, with mean volume of 4.16 ml (0.5-8 ml). All samples were culture-positive for Streptococcus pneumoniae. Comparing with control, all experimental groups presented reduction of larger than 135 nm molecular size, but there was only significant difference with alteplase (p = 0,02). Viscosity reduced at all experimental groups, but increased at control. DNase group presented negative median (-5 mPa/s) of viscosity, and differed significantly from that observed in the control group (p = 0.04).

Conclusions: Alteplase, DNase and alteplase + DNase changed significantly physical and chemical properties of experimental empyema at fibrinopurulent phase: alteplase reduced molecular size larger than 135 nm and DNase reduced viscosity.

Keywords: Alteplase; DNase; Dynamic light scattering; Empyema; Pleural effusion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Deoxyribonucleases / administration & dosage*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Empyema, Pleural / drug therapy*
  • Empyema, Pleural / physiopathology
  • Fibrinolytic Agents / administration & dosage*
  • Rats
  • Rats, Wistar
  • Tissue Plasminogen Activator / administration & dosage*
  • Treatment Outcome
  • Viscosity

Substances

  • Fibrinolytic Agents
  • Deoxyribonucleases
  • Tissue Plasminogen Activator