Abstract 167: Possible New Application of HTK Solution to Protect Cardiac Arrest--Induced Brain Injury After Cardiopulmonary Resuscitation
Background: The cardioplegic solution, histidine-ketoglutarate-tryptophan (HTK), is a preservative solution for organ transplantation. Here we tested whether HTK may protect neurons against poor oxygen-induced cell damage and thus alleviate ischemic injury in brain after CA.
Methods: The CA-mediated brain damage was induced by stop of ventilation for 4 min 30 sec (4’30’’) or 6 min 30 sec (6’30’’), and followed by manual CPR and epinephrine. HTK (200 μl) was given into brain via left carotid arterial catheter after CA. The sterile saline was given as controls. Neurological deficit scoring for motor function and mortality were evaluated on day 0 to 3 during recovery. The neuronal-like NG108-15 cells were applied and exposed to 2% oxygen or H2O2 to induce severe hypoxic (SH) injury or cytotoxicity in the presence or absence of HTK. Cell viability was assayed by the release of lactate dehydrogenase (LDH). Changes in caspase-3 activity for cell death were evaluated.
Results: Compared with the 6’30’’ CA groups, the 4’30’’ groups had higher survival rates despite either in saline- or HTK-treated rats after 3-day CA (5/8 of 4’30’’ vs. 4/15 for 6’30’’ in saline-treated groups; 6/8 of 4’30’’ vs. 4/9 for 6’30’’ in HTK-treated groups). Neurological scores were significantly improved by HTK on day 1 for the 4’30’’ groups and days 1-3 for the 6’30” group. Most of improvements in the HTK-treated rats were related to increases in level of conscious, corneal reflex, righting reflex, motor coordination, movement activity but not respiration. Compared to the untreated NG108-15 cells, replacement of culture medium with HTK attenuated SH- and H2O2- mediated cytotoxicity in a volume- and time-dependent manner. Interestingly, these effects were associated with reduction of caspase-3 activation.
Conclusion: These results suggest HTK is also an effective neuroprotective solution to protect neuron against hypoxia and treat CA-induced brain dysfunction via the mechanism of caspase-3 inhibition.
Author Disclosures: Y. Chen: None. M. Ma: None.
- © 2014 by American Heart Association, Inc.