Optimal inhaled oxygen and carbon dioxide concentrations for post-cardiac arrest cerebral reoxygenation and neurological recovery.

Prolonged cerebral hypoperfusion after the return of spontaneous circulation (ROSC) from cardiac arrest (CA) may lead to poor neurological recovery. In a 7-min asphyxia-induced CA rat model, four combinations of inhaled oxygen (iO2) and carbon dioxide (iCO2) were administered for 150 min post-ROSC and compared in a randomized animal trial. At the end of administration, the partial pressure of brain tissue oxygenation (PbtO2) monitored in the hippocampal CA1 region returned to the baseline for the 88% iO2 [ΔPbtO2, median: -0.39 (interquartile range: 5.6) mmHg] and 50% iO2 [ΔpbtO2, -2.25 (10.9) mmHg] groups; in contrast, PbtO2 increased substantially in the 88% iO2+12% iCO2 [ΔpbtO2, 35.05 (16.0) mmHg] and 50% iO2+12% iCO2 [ΔpbtO2, 42.03 (31.7) mmHg] groups. Pairwise comparisons (post hoc Dunn's test) indicated the significant role of 12% iCO2 in augmenting PbtO2 during the intervention and improving neurological recovery at 24 h post-ROSC. Facilitating brain reoxygenation may improve post-CA neurological outcomes.

Inhaled Carbon Dioxide Improves Neurological Outcomes by Downregulating Hippocampal Autophagy and Apoptosis in an Asphyxia-Induced Cardiac Arrest and Resuscitation Rat Model.

Background Protracted cerebral hypoperfusion following cardiac arrest (CA) may cause poor neurological recovery. We hypothesized that inhaled carbon dioxide (CO2) could augment cerebral blood flow (CBF) and improve post-CA neurological outcomes. Methods and Results After 6-minute asphyxia-induced CA and resuscitation, Wistar rats were randomly allocated to 4 groups (n=25/group) and administered with different inhaled CO2 concentrations, including control (0% CO2), 4% CO2, 8% CO2, and 12% CO2. Invasive monitoring was maintained for 120 minutes, and neurological outcomes were evaluated with neurological function score at 24 hours post-CA. After the 120-minute experiment, CBF was 242.3% (median; interquartile range, 221.1%-267.4%) of baseline in the 12% CO2 group while CBF fell to 45.8% (interquartile range, 41.2%-58.1%) of baseline in the control group (P<0.001). CBF increased along with increasing inhaled CO2 concentrations with significant linear trends (P<0.001). At 24 hours post-CA, compared with the control group (neurological function score, 9 [interquartile range, 8-9]), neurological recovery was significantly better in the 12% CO2 group (neurological function score, 10 [interquartile range, 9.8-10]) (P<0.001) while no survival difference was observed. Brain tissue malondialdehyde (P=0.02) and serum neuron-specific enolase (P=0.002) and S100ß levels (P=0.002) were significantly lower in the 12% CO2 group. TUNEL (terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling)-positive cell densities in hippocampal CA1 (P<0.001) and CA3 (P<0.001) regions were also significantly reduced in the 12% CO2 group. Western blotting showed that beclin-1 (P=0.02), p62 (P=0.02), and LAMP2 (lysosome-associated membrane protein 2) (P=0.01) expression levels, and the LC3B-II:LC3B-I ratio (P=0.02) were significantly lower in the 12% CO2 group. Conclusions Administering inhaled CO2 augmented post-CA CBF, mitigated oxidative brain injuries, ameliorated neuronal injury, and downregulated apoptosis and autophagy, thereby improving neurological outcomes.

A novel role for ß2-microglobulin: a precursor of antibacterial chemokine in respiratory epithelial cells.

We analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells (REC) upon activation by IL-1ß and different pathogen-associated molecular patterns. A 9 kDa fragment derived from ß2-microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary structure of sB2M-9 was revealed to increase its pI value that potentially could play an important role in innate defense. sB2M-9 exhibits antibacterial activity against Gram positive Staphylococcus aureus (SA) but not against Gram negative Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA clumps was significantly greater than that to SA without clumps. sB2M-9 binds to SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we demonstrated that REC release a novel chemokine with antibacterial activity that is shed from B2M to facilitate THP-1 migration.