Dennis F. Landers

Ischemic brain injury in vitro: protective effects of NMDA receptor antagonists and calmidazolium

Excessive Ca2+ influx through NMDA receptor-coupled channels has been linked to neuronal cell death. Using an in vitro model of transient brain ischemia, we investigated possible protective effects of NMDA receptor antagonists ketamine or MK-801 and of calmidazolium, an inhibitor of intracellular Ca2(+)-activated proteins. Brain ischemia/recovery was simulated in isolated hippocampal slices and injury monitored by measurement of ATP levels. Omission of both glucose and oxygen (but not oxygen alone) for 20 min led to persistent ATP deficits after 4 h recovery. Addition of ketamine or MK-801 at 1 microM permitted ATP to recover within 1 h, as did addition of calmidazolium at 10 microM. Our findings are consistent with other reports that NMDA receptor antagonists can protect neuronal tissue from ischemic damage. The role of inappropriately activated Ca2(+)-mediated signaling processes in the mechanism(s) of such injury is suggested by the protection also seen with calmidazolium, an inhibitor of calmodulin and other structurally related proteins such as calpain(s) and protein kinase C. The inhibition of intracellular Ca2+ target proteins may be an alternative for protection of the brain against injury due to insults that activate NMDA receptors.

Partitioning of vasoactive intestinal polypeptide into lipid bilayers

Incubation of radiolabeled vasoactive intestinal polypeptide (VIP) with preformed lipid vesicles composed of phosphatidylcholine, phosphatidylglycerol and cholesterol resulted in reversible and saturable association of the peptide with the lipid bilayer. The pH-optimum for the reaction was in the physiological range. The vesicle-associated peptide displayed enhanced stability to proteolytic digestion, it was efficiently released into the supernatant by detergent-solubilization of the vesicles but remained vesicle-associated during treatment with agents that disrupt ionic interactions. Peptide binding by electrically neutral vesicles was lower than that by negative vesicles. Electron spin resonance studies with 5-doxylstearic acid or 16-doxylstearic acid labeled vesicles suggested that VIP decreased the fluidity close to the surface of the bilayer and increased the fluidity in its hydrophobic core. These observations suggest that VIP can bind and penetrate lipid bilayers.

Plasma laudanosine levels in patients given atracurium during liver transplantation.

Atracurium, a nondepolarizing muscle relaxant, does not depend on the liver for clearance, but its principal metabolite, laudanosine, is eliminated primarily by the liver and is potentially neurotoxic. We measured atracurium and laudanosine levels in 15 adult patients during the three stages of liver transplantation to assess the effect of major impairment of liver function. Atracurium was given in a bolus dose of 0.5 mg/kg followed by continuous infusion at a rate adjusted to maintain 95–99% of total neuromuscular block, as judged by train of four response to facial nerve stimulation. Atracurium levels remained constant at 1.4--1.8 μg/mL during the 180-min preanhepatic and 75-min anhepatic stages but decreased to a mean of 1.0 μg/mL by the end of the 180-min postanhepatic stage. In contrast, laudanosine levels increased during each stage, being 0.40 ± 0.18, 0.50 ± 0.22, and 0.43 ± 0.16 μg/mL after the preanhepatic, anhepatic, and postanhepatic stages, respectively. The highest individual value recorded was 1.02 μg/mL. We conclude that, despite increases in laudanosine levels during each stage of liver transplantation in patients receiving atracurium, those levels are only about one-tenth of the maximum values previously reported in humans.

Management of a severed endotracheal tube during LeFort osteotomy

An unusual but serious case in which the endotracheal tube was severed during LeFort osteotomy is presented. The aspects of the surgery that can create this problem are reviewed. Past literature is reviewed, and various procedures for the management of this problem, including the plan followed in this case, are discussed.

Anesthetic management for the high-risk ophthalmic patient.

A 69-year-old white female presented for corneal transplant, but her numerous medical problems placed her at unacceptably high risk for prolonged general anesthesia. Routine monitored anesthesia care measures would not have provided her or the surgeon the comfort and repose necessary for a successful outcome. We describe anesthetic management for ophthalmic surgery, using epidural anesthesia in conjunction with retrobulbar block, in an elderly patient at high risk for general anesthesia whose intractable back and leg pain would have otherwise precluded her cooperation in maintaining a motionless operative field.

Unusual etiology of hyperkalemia in an immunocompromised patient

Hyperkalemia was found in an immunocompromised patient undergoing emergency cystoscopy. The cause of the hyperkalemia was an intraperitoneal rupture of the bladder. This case report discusses conditions that predispose patients to bladder rupture and anesthetic management of hyperkalemia.