Issn Print: 0265-0215

Publication Date: 2006/06/01


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The effects of drotrecogin alfa (activated) on the neurological outcome after cardiac arrest in rats: A-822

P. Teschendorf; M. Albertsmeier; E. Popp; P. Vogel; B. W. Boettiger

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Background and Goal of Study: Recent data indicate that the ischaemia reperfusion syndrome after whole body ischaemia following cardiac arrest (CA) shows similar pathological findings as septic patients (1). Drotregocin alfa (activated, rhAPC) is the first licensed drug to treat patients with severe sepsis (2). As neurological outcome plays a pivotal role after CA, we underwent the following study to examine the effects of rhAPC on neurological outcome after CA in rats.
Materials and Methods: After approval of the animal care committee, male wistar rats were subjected to 6 min CA (2). Following restoration of spontaneous circulation (ROSC) animals were randomized into three groups (n = 12): (1) high dose rhAPC (2mg/kg bolus, 0.1 mg/kg/h for 6h); (2) low dose rhAPC (0.5mg/kg bolus and 0.025mg/kg/h for 6h); (3) placebo (rat albumin). To assess the neurological outcome the Katz neurological deficit score (NDS) and a modified tape removal test (4) were applied pre CA and at 1, 3 and 7d after ROSC.
Results and Discussions: The NDS showed a clear neurological deficit in all groups with a significant recovery from 1d to 7d. The tape removal test also showed a marked neurological deficit in all groups at 1d. On 3d animals treated with low dose rhAPC removed the tapes significantly faster than placebo animals (24.8 vs. 48.0s; p = 0.013). This effect was no longer apparent at 7d after CA.
Conclusion(s): This study demonstrates for the first time positive effects of rhAPC on the neurological outcome after 6 min of CA in rats. Applying the tape removal test a significant improvement can be seen at 3d after ROSC. The lack of an effect at 7d after ROSC might be due to the delayed type of neuronal death after cardiac arrest.

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