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

Sophie Leahy,Mahnaz Shahidi,Norman P Blair,Shayan Farzad

doi:10.1038/s41598-020-67255-4

Abstract

Retinal functional, biochemical, and anatomical changes have been previously reported in long-term experimental permanent bilateral common carotid artery occlusion (BCCAO). The purpose of the current study was to investigate progressive reductions in retinal oxygen metabolism (MO2) due to inadequate compensation by oxygen delivery (DO2) and extraction fraction (OEF) after BCCAO. Twenty-nine rats were subjected to BCCAO and were imaged after 3 hours, 3 days, 7 days, or 14 days. Six rats underwent a sham procedure. Phosphorescence lifetime and blood flow imaging were performed in both eyes to measure retinal oxygen contents and total retinal blood flow, respectively. DO2, MO2, and OEF were calculated from these measurements. Compared to the sham group, DO2 and MO2 were reduced after all BCCAO durations. OEF was increased after 3 hours and 3 days of BCCAO, but was not different from the sham group after 7 and 14 days. Between 3 and 7 days of BCCAO, DO2 increased, OEF decreased, and there was no significant difference in MO2. These findings may be useful to understand the pathophysiology of retinal ischemia.

Highlights

Reported no retinal thinning and an increase in thickness of the outer plexiform layer (OPL) presumably due to edema
We demonstrated reduced DO2 and MO2 up to 14 days after bilateral common carotid artery occlusion (BCCAO)
By 7 to 14 days MO2 had stabilized at a reduced level and DO2 had reached a corresponding reduced value such that OEF approximated the normal value. Both DA and DV increased after 3 days and 7 days of BCCAO, indicating vasodilation of major retinal vessels in response to BCCAO

Summary

Introduction

Reported no retinal thinning and an increase in thickness of the outer plexiform layer (OPL) presumably due to edema. We have previously demonstrated that complete occlusion of the ophthalmic vessels followed by reperfusion results in reductions of total retinal blood flow (TRBF), oxygen delivery (DO2), and oxygen metabolism (MO2)[14]. We reported the effect of reductions in TRBF on DO2, MO2, and oxygen extraction fraction (OEF) immediately and after a few days of BCCAO15–17. There is lack of knowledge about alterations in DO2, MO2, and OEF due to long-term, incomplete reduction in TRBF (in our case long-term BCCAO), which is more relevant to clinical ischemic conditions than assessment of changes in these parameters immediately after complete loss of blood flow. The purpose of the current study was to test the hypothesis that long-term incomplete retinal ischemia by BCCAO causes progressive reductions of MO2 due to inadequate compensation by DO2 and OEF

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Conclusion