{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:59:36Z","timestamp":1789761576584,"version":"4.0.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Protracted cerebral hypoperfusion following cardiac arrest (CA) may cause poor neurological recovery. We hypothesized that inhaled carbon dioxide (CO\n              <jats:sub>2<\/jats:sub>\n              ) could augment cerebral blood flow (CBF) and improve post\u2010CA neurological outcomes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              After 6\u2010minute asphyxia\u2010induced CA and resuscitation, Wistar rats were randomly allocated to 4 groups (n=25\/group) and administered with different inhaled CO\n              <jats:sub>2<\/jats:sub>\n              concentrations, including control (0% CO\n              <jats:sub>2<\/jats:sub>\n              ), 4% CO\n              <jats:sub>2<\/jats:sub>\n              , 8% CO\n              <jats:sub>2<\/jats:sub>\n              , and 12% CO\n              <jats:sub>2<\/jats:sub>\n              . Invasive monitoring was maintained for 120\u2009minutes, and neurological outcomes were evaluated with neurological function score at 24 hours post\u2010CA. After the 120\u2010minute experiment, CBF was 242.3% (median; interquartile range, 221.1%\u2013267.4%) of baseline in the 12% CO\n              <jats:sub>2<\/jats:sub>\n              group while CBF fell to 45.8% (interquartile range, 41.2%\u201358.1%) of baseline in the control group (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). CBF increased along with increasing inhaled CO\n              <jats:sub>2<\/jats:sub>\n              concentrations with significant linear trends (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). At 24\u2009hours post\u2010CA, compared with the control group (neurological function score, 9 [interquartile range, 8\u20139]), neurological recovery was significantly better in the 12% CO\n              <jats:sub>2<\/jats:sub>\n              group (neurological function score, 10 [interquartile range, 9.8\u201310]) (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) while no survival difference was observed. Brain tissue malondialdehyde (\n              <jats:italic>P<\/jats:italic>\n              =0.02) and serum neuron\u2010specific enolase (\n              <jats:italic>P<\/jats:italic>\n              =0.002) and S100\u03b2 levels (\n              <jats:italic>P<\/jats:italic>\n              =0.002) were significantly lower in the 12% CO\n              <jats:sub>2<\/jats:sub>\n              group. TUNEL (terminal deoxynucleotidyl transferase\u2013mediated biotin\u2013deoxyuridine triphosphate nick\u2010end labeling)\u2010positive cell densities in hippocampal CA1 (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and CA3 (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) regions were also significantly reduced in the 12% CO\n              <jats:sub>2<\/jats:sub>\n              group. Western blotting showed that beclin\u20101 (\n              <jats:italic>P<\/jats:italic>\n              =0.02), p62 (\n              <jats:italic>P<\/jats:italic>\n              =0.02), and LAMP2 (lysosome\u2010associated membrane protein 2) (\n              <jats:italic>P<\/jats:italic>\n              =0.01) expression levels, and the LC3B\u2010II:LC3B\u2010I ratio (\n              <jats:italic>P<\/jats:italic>\n              =0.02) were significantly lower in the 12% CO\n              <jats:sub>2<\/jats:sub>\n              group.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Administering inhaled CO\n              <jats:sub>2<\/jats:sub>\n              augmented post\u2010CA CBF, mitigated oxidative brain injuries, ameliorated neuronal injury, and downregulated apoptosis and autophagy, thereby improving neurological outcomes.\n            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