The role of the monosialoganglioside, GM1 as a neuroprotectant in an experimental model of cardiopulmonary bypass and hypothermic circulatory arrest.
Twelve male dogs were placed on closed-chest cardiopulmonary bypass, subjected to 2 h of HCA at 18 degrees C, and rewarmed to 37 degrees C on closed-chest cardiopulmonary bypass. All animals were mechanically ventilated and monitored for 20 h before extubation and survived for 3 days. Group 1 dogs (n = 6) were pretreated with GM1, 30 mg/kg/24 h for 3 days before HCA, and received continuous infusion of GM1 during the procedure and 30 mg/kg/24 h for 3 days after HCA. Group 2 dogs (n = 6) received vehicle only. With a species-specific behavior scale that yielded a neurodeficit score ranging from 0% (normal) to 100% (brain dead), all animals were neurologically assessed every 12 h by two observers. After death at 72 h, brains were examined by glutamate receptor autoradiography and by histologic examination for patterns of selective neuronal necrosis and were scored blindly from 0 (normal) to 100 (severe injury). These results provide evidence of a role for GE in the development of HCA-induced brain injury and suggest that monosialogangliosides may have a neuroprotective effect in prolonged periods of HCA.
Johns Hopkins Hospital, Baltimore, Maryland 21287-4618, USA. WBaumgar@csurg.jhmi.jhu.edu
W A
WA
Baumgartner
J M
JM
Redmond
K J
KJ
Zehr
M V
MV
Brock
E E
EE
Tseng
M E
ME
Blue
J C
JC
Troncoso
M V
MV
Johnston
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001926:Brain Death; D002315:Cardiopulmonary Bypass; D004285:Dogs; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000627:therapeutic use*; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D007262:Infusions, Intravenous; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015424:Reperfusion
D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D005677:G(M1) Ganglioside