Magnetic resonance spectroscopy for evaluation of liposome-encapsulated hemoglobin as a resuscitation fluid.
Liposome-encapsulated hemoglobin (LEH) based on a novel, synthetic, non-phospholipid was developed, and evaluated for cerebral energy metabolism in a 40% hemorrhage rat model. The markers of tissue energetics were monitored by (1)H- and (31)P-magnetic resonance spectroscopy (MRS). After hemorrhage, (1)H-MRS showed an increase in the levels of lactate and pyruvate. These markers returned to baseline values following LEH resuscitation. Both LEH and saline were able to exert a neuron-protective effect as indicated by the recovery of N-acetylaspartate. (31)P MRS showed a fall in phosphocreatine after hemorrhage, which upon LEH or saline resuscitation returned to the baseline values. Similarly, inorganic phosphate increased after bleeding, but returned to normal after resuscitation. LEH resuscitation also recovered beta-ATP levels, but saline resuscitation provided only a modest recovery. The results indicate the utility of MRS to monitor cerebral metabolism in hemorrhage/resuscitation. The data is also supportive of the new LEH formulation as an oxygen carrier.
Awasthi
Vibhudutta
V
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA. vawasthi@ouhsc.edu
Agashe
H
H
Doblas
S
S
Towner
R
R
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000628:therapy*; D004339:Drug Compounding / Q000009:adverse effects; D004734:Energy Metabolism / Q000187:drug effects; D005240:Feasibility Studies; D006454:Hemoglobins / Q000008:administration & dosage* / Q000138:chemical synthesis; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008081:Liposomes; D021061:Liquid Ventilation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D006454:Hemoglobins; D008081:Liposomes; D018696:Neuroprotective Agents; D001224:Aspartic Acid; D019344:Lactic Acid; D019289:Pyruvic Acid; C000179:N-acetylaspartate