PB0185 - Treatment of Advanced Stage Infectious or Traumatic Pleural Injuries with Lytic Therapy

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

GF

Galina Florova, PhD

Professor
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler, TX
Tyler, Texas, United States

Co-Author(s)

CD

Christian Jordan De Vera

Research Associate
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler
Tyler, Texas, United States
AA

Ali O. Azghani

Professor
Department of Biology, The University of Texas at Tyler, TX
Tyler, Texas, United States
RE

Rebekah L. Emerine

Research Associate
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler
Tyler, Texas, United States
JJ

Jincy Jacob

Research Associate
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler, TX
Tyler, Texas, United States
SC

Sunil Christudas

Post-Doctoral Researcher
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler
Tyler, Texas, United States
KS

Krishna Sarva

Research Associate
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler
Tyler, Texas, United States
JF

Jon M. Florence

Research Associate
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler, TX
Tyler, Texas, United States
SI

Steven Idell

Professor
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler, TX
Tyler, Texas, United States
AK

Andrey A. Komissarov

Professor
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler, TX
Tyler, Texas, United States

Background: Models of pleural injury in rabbits; the advanced Streptococcus pneumoniae-induced empyema and retained hemothorax recapitulate clinical and biochemical characteristics of the human pleural conditions.

Aims: We hypothesized that these models can be employed for testing treatment with human single chain (sc) urokinase (scuPA) or tissue type plasminogen activator (sctPA).

Methods: Females New Zealand White rabbits were used to induce either infectious or traumatic pleural injuries. These injuries were developed during 7d and were treated with two injections (8h apart) of sctPA or scuPA via the chest tube. The outcomes of the therapy were assessed at 24h by gross imaging, ultrasonography, computed tomography (CT), histology, and a battery of biochemical methods. Therapy for empyema was considered successful if Gross Lung Injury Score (GLIS) at 24 h after the treatment was ≤10. Successful therapy of retained hemothorax was associated with the efficient drainage as measured by CT and significant decrease of the clot size.

Results: While two injections of sctPA (1.0 mg/kg) were successful in treatment of either advanced empyema or retained hemothorax models in rabbits, scuPA (1.0 mg/kg) was more efficient in treatment of retained hemothorax, decreasing clot size and improving drainage.
Pleural fluid levels of active PAI-1 were decreased at both 8 and 24h suggesting that endogenous PAI-1 inhibits a significant fraction of exogenous plasminogen activators in both models.

Conclusion(s): Novel rabbit models of empyema and retained hemothorax are amenable to lytic interventions with human fibrinolysins. Both models are amendable for validation of molecular targets and testing of novel targeted approaches to increase efficacy of lytic therapy.

This work is funded by NHLBI R33 HL154103 (SI, GF, AAK) and R01HL130402 (GF, SI, AAK).