Sepsis in sheep reduces pulmonary microvascular sieving capacity

Area of Science:

• Pulmonary physiology
• Microvascular research
• Sepsis pathophysiology

Background:

• Pulmonary microvascular permeability is crucial for lung function.
• Sepsis can significantly alter vascular integrity.
• Understanding sepsis-induced changes in lung permeability is vital for treatment.

Purpose of the Study:

• To investigate the impact of live Escherichia coli infusion on pulmonary microvascular permeability in sheep.
• To quantify changes in osmotic reflection coefficients and equivalent pore dimensions.
• To determine the role of pore size and number alterations in sepsis-related lung injury.

Main Methods:

• Preparation of chronic lung lymph fistula in seven sheep.
• Measurement of osmotic reflection coefficients (sigma) for total protein, albumin, IgG, and IgM.
• Calculation of equivalent pore dimensions before and after E. coli infusion.
• Assessment of filtration independent L/P values and lymph to plasma protein concentration ratios.

Main Results:

• Pre-sepsis sigma values for total protein, albumin, IgG, and IgM were 0.73, 0.65, 0.76, and 0.91, respectively.
• Equivalent pore radii were 50 Å (small) and 175 Å (large), with 35% filtration via large pores.
• Post-sepsis, sigma values decreased significantly (0.58, 0.50, 0.64, 0.83).
• Large pore radius increased to 200 Å, accounting for 49% of flow, with a 32% increase in large pore number.

Conclusions:

• Live Escherichia coli infusion significantly increases pulmonary microvascular permeability in sheep.
• Sepsis alters lung microvasculature by increasing the size and number of large pores.
• These findings highlight the dynamic changes in lung barrier function during sepsis.