Fructose-1,6-bisphosphate and MK-801 by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 min in dogs. An exploratory study

In our exsanguination cardiac arrest (CA) outcome model in dogs we are syst ematically exploring suspended animation (SA), i.e. preservation of brain a nd heart immediately after the onset of CA to enable transport and resuscit ative surgery during CA, followed by delayed resuscitation. We have shown i n dogs that inducing moderate cerebral hypothermia with an aortic arch flus h of 500 ml normal saline solution at 4 degreesC, at start of CA 20 min no- flow, leads to normal functional outcome. We hypothesized that, using the s ame model, but with the saline flush at 24 degreesC inducing minimal cerebr al hypothermia (which Would be more readily available in the field), adding either fructose-1,6-bisphosphate (FBP, a more efficient energy substrate) or MK-801 (an N-Methyl-D-aspartate (NMDA) receptor blocker) would also achi eve normal functional outcome. Dogs (range 19-30 kg) were exsanguinated ove r 5 min to CA of 20 min no-flow, and resuscitated by closed-chest cardiopul monary bypass (CPB). They received assisted circulation to 2 h, mild system ic hypothermia (34 degreesC) post-CA to 12 h, controlled ventilation to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received an aortic arc h flush of 500 ml saline at 24 degreesC by a balloon-tipped catheter, inser ted through the femoral artery (control group, n=6). In the FBP group (n=5) , FBP (total 1440 or 4090 mg/kg) was given by flush and with reperfusion. I n the MK-801 group (n=5), MK-801 (2, 4, or 8 mg/kg) was given by flush and with reperfusion. Outcome was assessed in terms of overall performance cate gories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, com a; 5, brain death or death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain death), and brain histologic damage scores (HDS, total HDS 0, n o damage; >100, extensive damage; 1064, maximal damage). In the control gro up, one dog achieved OPC 2, one OPC 3, and four OPC 4; in the FBP group, tw o dogs achieved OPC 3, and three OPC 4; in the MK-801 group, two dogs achie ved OPC 3, and three OPC 4 (P=1.0). Median NDS were 62% (range 8-67) in the control group; 55% (range 34-66) in the FBP group: and MIX, (range 26-59) in the MK-801 group (P=0.2). Median total HDS were 130 (range 56-140) in th e control group; 96 (range 64-104) in the FBP group; and 80 (range 34-122) in the MK-801 group (P=0.2). There was no difference in regional HDS betwee n groups. We conclude that neither FBP nor MK-801 by aortic arch Rush at th e start of CA, plus an additional i.v. infusion of the same drug during rep erfusion, can provide cerebral preservation during CA 20 min no-flow. Other drugs and drug-combinations should be tested with this model in search for a breakthrough effect. (C) 2001 Elsevier Science Ireland Ltd. All rights r eserved.