Isolated lung perfusion with Adriamycin. A preclinical study.

Area of Science:

• Cardiovascular Surgery
• Thoracic Surgery
• Pharmacology

Background:

• Isolated in vivo single-lung perfusion is a complex procedure.
• Assessing the toxicity of chemotherapeutic agents like Adriamycin (Adr) during perfusion is crucial for clinical application.

Purpose of the Study:

• To evaluate the safety and toxicity of isolated single-lung perfusion with Adriamycin in a large animal model.
• To determine an optimal Adriamycin dosage for single-lung perfusion with minimal adverse effects.

Main Methods:

• Single-lung perfusion was performed in dogs using an Adriamycin-containing whole-blood perfusate.
• Dogs underwent contralateral pneumonectomy two weeks post-perfusion to assess survival and toxicity.
• Histological examination was conducted on surviving animals.

Main Results:

• Initial groups (I and II) experienced high mortality, providing data on perfusion techniques and drug delivery.
• Group III dogs (n=5) perfused for 45 minutes with Adriamycin at 0.5 µg/ml survived pneumonectomy.
• Peak Adriamycin lung tissue levels were 3.8 ± 1.06 µg/g, with only mild focal fibrosis observed histologically.

Conclusions:

• Isolated single-lung perfusion is a reproducible and safe technique.
• A specific Adriamycin dosage was identified that demonstrates no apparent toxicity in this large animal model.
• These findings support the initiation of a clinical trial for Adriamycin lung perfusion.