Retinal Oxygen Delivery, Metabolism, and Extraction Fraction During Long-term Bilateral Common Carotid Artery Occlusion in Rats

Abstract

Purpose : Although functional, biochemical, and anatomical changes have been reported in long-term ischemia rodent models, research regarding changes in oxygen metabolism is limited. The purpose of this study was to test the hypothesis that impairments of retinal oxygen delivery (DO₂), metabolism (MO₂) and extraction fraction (OEF) occur and are sustained with prolonged ischemia.

Methods : Retinal ischemia was induced in 24 rats by permanent bilateral ligation of common carotid arteries and 8 rats underwent sham procedures. Phosphorescence lifetime, microsphere fluorescence, and reflectance images were acquired in both eyes to measure retinal vascular oxygen tension, venous blood velocity and vessel diameter, respectively. Retinal arterial and venous oxygen contents (O_2A, O_2V), arteriovenous oxygen content difference (O_2AV), and total retinal blood flow (TRBF) were determined. We calculated: DO₂ = TRBF x O_2A, MO₂ = TRBF x O_2AV, and OEF = MO₂/DO₂. Data from individual eyes were available in 4 study groups according to duration of ischemia: 3 hours (3H; N=10), 3 days (3D; N=10), 7 days (7D; N=14), and 14 days (14D; N=10) and one sham group (N=14; combined 3 days, 7 days, 14 days sham groups). DO₂, MO_2, and OEF were compared by linear mixed models accounting for data obtained in fellow eyes.

Results : In the sham group, DO₂, MO₂, and OEF were 814±172 nLO₂/min, 403±121 nLO₂/min, and 0.50±0.12 respectively. DO₂ was lower in 3H (β = -711 nLO₂/min), 3D (β = -575 nLO₂/min), and 7D (β = -294 nLO₂/min) groups compared to the sham group (P<0.003). MO₂ was lower in 3H (β = -294 nLO₂/min), 3D (β = -179 nLO₂/min), and 7D (β = -136 nLO₂/min) groups compared to the sham group (P<0.01). In the 14D group, DO₂ (β = -184 nLO₂/min) and MO₂ (β = -46 nLO₂/min) were not significantly different from the sham group (P>0.09). OEF was higher in 3H (β = 0.49) and 3D (β = 0.44) groups compared to the sham group (P<0.001). OEF was not significantly different in 7D (β = 0.09) and 14D (β = 0.13) groups compared to the sham group (P>0.11).

Conclusions : Permanent bilateral common carotid occlusion significantly, but not totally, impairs DO₂, MO₂ and OEF, but these recover within 14 days. This model may be useful to identify the characteristics of recoverable tissue with ischemia.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.