TY - JOUR
T1 - Effects of the nitric oxide donor 3-morpholinosydnonimine (SIN-1) in focal cerebral ischemia dependent on intracellular brain pH
AU - Coert, Bernard A.
AU - Anderson, Robert E.
AU - Meyer, Fredric B.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Object. A nitric oxide (NO) donor that has been successfully used in the treatment of myocardial infarction, 3-morpholinosydnonimine (SIN-1), may be a potential neuroprotective agent. Production of NO in brain microsomes is dependent on the pH. The purpose of this study was to determine the efficacy of SIN-1 and its dependence on pH in vivo during periods of focal cerebral ischemia. Methods. At 0.1 or 1 mg/kg, SIN-1 was administered to 54 Wistar rats 30 minutes before a 2-hour period of focal cerebral ischemia under moderate hypo-, normo-, and hyperglycemic conditions. Measurements of brain intracellular pH (pHi); regional cortical blood flow, and the redox state of nicotinamide adenine dinucleotide were obtained in three additional animals to confirm the effects of the serum glucose manipulations. The animals were killed at 72 hours after the ischemic period to obtain infarction volumes. Administration of SIN-1 significantly reduced infarction in normoglycemic animals and, to a lesser extent, in hyperglycemic animals, indicating that SIN-1 was less effective under hyperglycemic conditions. At either dose SIN-1 had no significant effect on infarction volume in moderately hypoglycemic animals because moderate hypoglycemia in itself significantly (p < 0.005) reduced infarction volume. Conclusions. The NO donor SIN-1 may be a useful intraoperative cerebral protective agent. Furthermore, it is hypothesized that a mechanism that could explain the published discrepancies regarding the effects of NO donors in vivo may be affected by differences in ischemic brain acidosis.
AB - Object. A nitric oxide (NO) donor that has been successfully used in the treatment of myocardial infarction, 3-morpholinosydnonimine (SIN-1), may be a potential neuroprotective agent. Production of NO in brain microsomes is dependent on the pH. The purpose of this study was to determine the efficacy of SIN-1 and its dependence on pH in vivo during periods of focal cerebral ischemia. Methods. At 0.1 or 1 mg/kg, SIN-1 was administered to 54 Wistar rats 30 minutes before a 2-hour period of focal cerebral ischemia under moderate hypo-, normo-, and hyperglycemic conditions. Measurements of brain intracellular pH (pHi); regional cortical blood flow, and the redox state of nicotinamide adenine dinucleotide were obtained in three additional animals to confirm the effects of the serum glucose manipulations. The animals were killed at 72 hours after the ischemic period to obtain infarction volumes. Administration of SIN-1 significantly reduced infarction in normoglycemic animals and, to a lesser extent, in hyperglycemic animals, indicating that SIN-1 was less effective under hyperglycemic conditions. At either dose SIN-1 had no significant effect on infarction volume in moderately hypoglycemic animals because moderate hypoglycemia in itself significantly (p < 0.005) reduced infarction volume. Conclusions. The NO donor SIN-1 may be a useful intraoperative cerebral protective agent. Furthermore, it is hypothesized that a mechanism that could explain the published discrepancies regarding the effects of NO donors in vivo may be affected by differences in ischemic brain acidosis.
KW - 3-Morpholinosydnonimine
KW - Focal cerebral ischemia
KW - Intracellular brain pH
KW - Nitric oxide
KW - Nitric oxide donor
KW - Rat
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U2 - 10.3171/jns.2002.97.4.0914
DO - 10.3171/jns.2002.97.4.0914
M3 - Article
C2 - 12405381
AN - SCOPUS:0036801580
SN - 0022-3085
VL - 97
SP - 914
EP - 921
JO - Journal of neurosurgery
JF - Journal of neurosurgery
IS - 4
ER -