Chronic Obstructive Pulmonary Disease (COPD) Model

Purpose

To induce COPD in a rodent model and assess the efficacy of new compounds.

 


Method

  • COPD will be induced in rats by intratracheal instillation of LPS followed by exposure to cigarette smoke.
  • Respiratory function will be assessed weekly by whole-body plethysmography. At each time point, breathing frequency (Bf), tidal volume, and enhanced pause (Penh) will be recorded, reflecting the changes in the waveform of the box pressure signal from both inspiration and expiration, related to early and late expiration.
  • Blood can be drawn at different time points for compound and cytokines plasma level quantification. Blood volumes will be limited to 800 µL per week to avoid hypovolumia.

 

Study outcome

  • Whole-body plethysmograph (respiratory function; pulmonary resistance (PenH); sneezing);
  • Changes in cytokine levels and cell counts measured in plasma and BALF (IL6, IL8 and TNF-a);
  • Changes in mean arterial pressure, and heart rate (HR);
  • O2 saturation, ECG intervals;
  • Ventilation pressure, volume, frequency; and
  • Semi-quantitative and clinical histological analysis based on pulmonary emphysema and vascular remodeling performed independently by two pulmonary histopathologists.

Compliance

Non-GLP compliant. The study is generally used in discovery-phase preclinical research.

 


Species

Rats

Charles-E. Laurent

Ph.D., Director of In-Vivo Pharmacology

“Over the past 13 years, I had the greatest opportunity to exploit my passion for science at IPST by contributing to the design, and validation of unique assays which are now routinely run and serve to quantify the efficacy in preclinical drug candidates. My greatest contribution was to see the increase in demand for efficacy services such as the rodent model of pulmonary arterial hypertension (PAH), as well as our intravascular thrombosis and hemostasis models.” Charles completed his doctorate in Pharmacology at the Université de Montreal followed by 4 years of post doctorate studies at the University of Pittsburgh in the Department of Molecular Genetics and Biochemistry. His field of expertise includes cardiovascular pharmacology and molecular biology.