Clinical Assessment of an Ipsilateral Cervical Spinal Nerve Block for Prosthetic Laryngoplasty in Anesthetized Horses.

The nociceptive blockade of locoregional anesthesia prior to surgical stimulation can decrease anesthetic agent requirement and thereby potential dose-dependent side effects. The use of an ipsilateral second and third cervical spinal nerve locoregional anesthetic block for prosthetic laryngoplasty in the anesthetized horses has yet to be described. Anesthetic records of 20 horses receiving locoregional anesthesia prior to laryngoplasty were reviewed and compared to 20 horses of a similar patient cohort not receiving locoregional anesthesia. Non-blocked horses were 11 times more likely to require adjunct anesthetic treatment during surgical stimulation (P = 0.03) and were 7.4 times more likely to receive partial intravenous anesthesia in addition to inhalant anesthesia (P = 0.01). No horse in the blocked group received additional sedation/analgesia compared to the majority of non-blocked horses (75%) based on the anesthetist's perception of anesthetic quality and early recovery movement. No difference in recovery quality was observed between groups (P > 0.99). Cervical spinal nerve locoregional anesthesia appears well-tolerated and useful in reducing cumulative anesthetic agent requirement and may decrease the need for additional sedation/analgesia in horses undergoing anesthetized prosthetic laryngoplasty.

AICAR Administration Attenuates Hemorrhagic Hyperglycemia and Lowers Oxygen Debt in Anesthetized Male Rabbits.

Background: Many strategies have been utilized to treat traumatic shock via improved oxygen delivery (DO2), while fewer have been used to in an attempt to reduce oxygen demand (VO2). The cellular energy sensor 5' adenosine monophosphate-activated protein kinase (AMPK) has the potential to modulate both whole-body DO2 and VO2. Therefore, we determined the effect of the AMPK activator AICAR (5-aminoimidazole-4-carboxamide 1-ß-D-ribonucleoside) given acutely or chronically on key metabolites, hemodynamics, and oxygen consumption/delivery before and during hemorrhage in anesthetized male rabbits. Methods: Chronically treated animals received AICAR (40 mg/kg/day, IV) for 10 days prior to hemorrhage, while rabbits in the acute study were infused with AICAR (7.5 mg/kg bolus, 2 mg/kg/min infusion) or vehicle (0.3 ml/kg saline bolus, 0.03 ml/kg/min infusion) IV for 2 h prior to severe hemorrhage. Both acutely and chronically treated animals were sedated (ketamine/xylazine cocktail) the morning of the terminal experiment and surgically prepared for hemorrhage, including the implantation of arterial and venous catheters (for blood removal/sampling and drug/vehicle administration) and thoracotomy for implantation of transit-time flow transducers (for cardiac output determination). Results: AICAR given acutely lowered arterial blood glucose and increased blood lactate levels before hemorrhage, and abolished the well-documented hemorrhage-induced hyperglycemia seen in vehicle treated animals. Animals given AICAR chronically had blunted hemorrhage-induced hyperglycemia without prior baseline changes. Chronically treated AICAR animals showed significantly lower lactate levels during hemorrhage. Rabbits receiving AICAR both acutely and chronically experienced similar falls in mean arterial pressure, cardiac output and hence DO2 to their vehicle counterparts throughout the hemorrhage period. However, rabbits treated either acutely or chronically with AICAR accumulated lower oxygen deficits and debt during hemorrhage compared to vehicle-infused controls. Conclusions: The oxygen debt data suggest that AMPK activation could decrease trauma associated morbidity and mortality, perhaps by mechanisms related to increased glucose utilization. Additional studies are needed to investigate the effects of AICAR and associated mechanisms of action when given during resuscitation from hemorrhage.

Targeted lipidomics distinguishes patient subgroups in mild cognitive impairment (MCI) and late onset Alzheimer's disease (LOAD).

BACKGROUND: Diverse research approaches support the concept that a clinical diagnosis of Late-Onset Alzheimer's Disease (LOAD) does not distinguish between subpopulations with differing neuropathologies, including dementia patients with amyloid deposition and dementia patients without amyloid deposition but with cortical thinning. Mild cognitive impairment (MCI) is generally considered the prodromal phase for LOAD, however, while a number of studies have attempted to define plasma biomarkers for the conversion of MCI to LOAD, these studies have not taken into account the heterogeneity of patient cohorts within a clinical phenotype. METHODS: Studies of MCI and LOAD in several laboratories have demonstrated decrements in ethanolamine plasmalogen levels in plasma and brain and increased levels of diacylglycerols in plasma and brain. To further extend these studies and to address the issue of heterogeneity in MCI and LOAD patient groups we investigated the levels of diacylglycerols and ethanolamine plasmalogens in larger cohorts of patients utilizing, high-resolution (0.2 to 2 ppm mass error) mass spectrometry. RESULTS: For the first time, our lipidomics data clearly stratify both MCI and LOAD subjects into 3 different patient cohorts within each clinical diagnosis. These include i) patients with lower circulating ethanolamine plasmalogen levels; ii) patients with augmented plasma diacylglycerol levels; and iii) patients with neither of these lipid alterations. CONCLUSIONS: These represent the first serum biochemical data to stratify MCI and LOAD patients, advancing efforts to biochemically define patient heterogeneity in cognitive disorders. GENERAL SIGNIFICANCE: Lipidomics offers a new approach for identifying biomarkers and biological targets in cognitive disorders.