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

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 (Mo 2) due to inadequate compensation by oxygen delivery (Do 2) and extraction fraction (oef) after BccAo. twentynine 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. DO 2 , Mo 2 , and oef were calculated from these measurements. compared to the sham group, Do 2 and Mo 2 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, DO 2 increased, oef decreased, and there was no significant difference in MO 2. These findings may be useful to understand the pathophysiology of retinal ischemia.

Retinal Degeneration in a Murine Model of Retinal Ischemia by Unilateral Common Carotid Artery Occlusion

“…However, well-developed collateral circulation has chances to prevent this phenomenon in humans [6,34]. Experimentally, to induce ocular ischemia, bilateral occlusions of CCAs were applied to adult rats due to their well-developed collateral circulation [8][9][10]. Adult black mice (C57BL/6) could not be subjected to bilateral occlusions of CCAs in that they die during/after the surgery [11,20], of which outcome is related to a lack of the complete Circle of Willis in adult black mice (especially, the missing of the posterior communicating artery) [35][36][37].…”

“…To date, there are limited experimental animal models for retinal degeneration in OIS. Using bilateral occlusions of CCAs, rats have been widely used for understanding the pathological mechanism for retinal degeneration in OIS [8][9][10]. Relatively, mice have not been commonly utilized, as there exist the limitations for the model development using bilateral occlusions of CCAs [11,12].…”

Retinal Oxygen Delivery and Metabolism Response to Hyperoxia During Bilateral Common Carotid Artery Occlusion in Rats

“…These timepoints were chosen based on our previous studies that demonstrated impairments in oxygen metrics after these durations of BCCAO. 46 – 48 After each duration of BCCAO, a randomly selected eye in each rat was imaged during two fractions of the inspired oxygen (FiO 2 ) condition: first under 21% O 2 inspiration (spontaneous room air breathing [RA]) and then immediately after 15 minutes of 100% O 2 inspiration (hyperoxia). Eight of the rats in the 30-minute BCCAO group were also imaged prior to BCCAO (baseline).…”

“…The common carotid arteries were accessed via a midline prelaryngeal incision, dissected from the sympathetic and vagus nerves and ligated, as previously described. 47 , 48 …”

“…We have previously reported reduced total retinal blood flow (TRBF), inner retinal oxygen delivery (DO 2 ) and oxygen metabolism (MO 2 ), and increased oxygen extraction fraction (OEF) both 30 minutes 46 and 3 days 47 , 48 after ischemia in rats induced by permanent bilateral common carotid artery occlusion (BCCAO). However, there is limited knowledge of these measurements in response to hyperoxia after the induction of retinal ischemia and specifically how responses to hyperoxia may change dependent on ischemia duration.…”