Oxygen Transport Impairment in the Failing Heart: A Histology-Image-Based Computational Analysis

Area of Science:

• Cardiovascular Research
• Biomedical Engineering
• Pathophysiology

Background:

• Reactive interstitial fibrosis (RIF) is a common finding in heart failure (HF).
• RIF involves interstitial space enlargement and collagen accumulation, impacting cardiac structure and function.
• The precise effect of these changes on oxygen (O2) transport to cardiomyocytes in HF remains unclear.

Purpose of the Study:

• To investigate the impact of interstitial space enlargement and RIF on oxygen transport from capillaries to cardiomyocytes in HF.
• To quantify the relationship between interstitial fibrosis, interstitial space, and tissue oxygenation in the myocardium.

Main Methods:

• Developed a histology-image-based computer modeling approach.
• Estimated the spatial profile of partial pressure of oxygen (pO2) in myocardial tissue samples.
• Analyzed samples from healthy dogs and dogs with experimentally induced HF.

Main Results:

• Both interstitial space enlargement and RIF significantly limit myocardial tissue oxygenation.
• Cardiomyocytes in HF dogs exhibited a ~47% lower pO2 compared to normal dogs.
• Severe RIF-induced hypoxia is driven by interstitial space enlargement, while mild/moderate RIF hypoxia is driven by altered oxygen diffusion and consumption rates.
• Cardiomyocyte pO2 significantly decreased with increasing interstitial area fraction (IAF) and increased with capillary area fraction (CAF).
• The CAF/IAF ratio effectively predicted tissue oxygenation (R²=0.824, p<0.0001).

Conclusions:

• Interstitial space enlargement and RIF substantially impair O2 transport from capillaries to cardiomyocytes in HF.
• These impairments can lead to significant regional tissue hypoxia in the heart.
• The findings highlight the critical role of interstitial remodeling in HF pathophysiology and oxygen supply.