Abstract 76: Blockade of Nitric Oxide Synthase during Reperfusion after Cardiac Arrest is Essential
Introduction: Ischemic-anoxic cerebral injury is among the leading courses of both mortality and morbidity after cardiac arrest and CPR. Only lately the prospects for cardiac arrest victims have improved due to implementation of hypothermia (HT) in the post-arrest care. Since long also search for pharmacological agents with neuroprotective effects has been done. Increasingly it has been recognized that the chances of finding a targeted single agent that blocks development of ischemic injury are meager. Due to this insight it has been increasingly important to find either a single drug with multimodal effects, or a combination of drugs being able to prevent or even reverse the development of the ischemic-anoxic injury.
Hypothesis: Hypothermia and pharmacological neuroprotective agents function by influencing different subcellular targets.
Methods: In order to elucidate mechanisms of action of on one hand therapeutical 34–32°C HT and, on the other hand, some drugs having been proven experimentally to possess neuroprotective effects we have compared neuropathological findings with those resulting from whole genome transcriptional analysis in brains of 20 piglets subjected to 12 min of untreated ventricular fibrillation, 8 min CPR and spontaneous reperfusion during 3h. Our study has been concentrated on cortical cerebral tissue.
Results: Our findings indicate that the brain-blood barrier is disrupted already after 5 min of untreated cardiac arrest. This leakage is less after induced HT as well as after administration of methylene blue (MB, an inhibitor of nitric oxide synthase and of guanylate cyclase) and S-PBN (a so-called spin trap scavenger). Similarly, in the early phase of reperfusion we find enhanced immunostaining of nitric oxide synthase in control experiments (without increased transcriptional activity of the corresponding genes) that, after use of HT, MB and S-PBN, is significantly reduced.
Conclusion: Immunostaing of nitric oxide synthase is significantly enhanced during reperfusion after cardiac arrest and CPR. Blockade of nitric oxide synthase seems to be an underestimated mechanism of neuroprotection after CPR.