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Biomedical subjects

L N Milde

Publications and source records attributed to L N Milde.

23 records · Page 2Linked to original sources
PubMed1987

The detrimental effect of lidocaine on cerebral metabolism measured in dogs anesthetized with isoflurane.

Previous studies in dogs have demonstrated that massive doses of intravenous lidocaine (160 mg X kg-1) can inhibit cerebral oxygen metabolism to a greater degree when administered with pentobarbital than can pentobarbital alone. From these data, it was hypothesized that lidocaine decreases cerebral metabolism by two means: suppression of cortical electrical activity and stabilization of neuronal membranes, and it was suggested that lidocaine might provide protection for the ischemic brain. In an attempt to apply this property clinically, the effect of a lower, clinically tolerated dose of lidocaine (15 mg X kg-1) on cerebral oxygen metabolism and cerebral blood flow was examined in dogs receiving deep isoflurane anesthesia. Once maximal metabolic suppression, as reflected by an isoelectric EEG, was achieved with isoflurane (3% end-expired), the administration of this dose of lidocaine had little effect on cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2). The CBF was 94 +/- 19 ml X min-1 X 100 g-1 during 3% isoflurane anesthesia, and was 102 +/- 11 ml X min-1 X 100 g-1 with the addition of lidocaine. The CMRO2 was 2.32 +/- 0.23 ml X min-1 X 100 g-1 during isoflurane anesthesia, and was 2.18 +/- 0.09 ml X min-1 X 100 g-1 following the administration of lidocaine. However, this dose of lidocaine did produce a derangement of cerebral metabolites. The cerebral concentration of ATP during 3% isoflurane anesthesia was 2.07 +/- 0.04 mumol X g-1 (cerebral ATP in normal unanesthetized dogs is 2.01 +/- 0.01 mumol X g-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Delayed treatment with nimodipine improves cerebral blood flow after complete cerebral ischemia in the dog.

Ten minutes of complete cerebral ischemia was produced in 18 dogs by temporary ligation of the aorta and venae cavae. Dogs were randomly assigned to one of three groups. A bolus dose of 10 micrograms kg-1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 microgram kg-1 min-1 was given at 15, 30, or 60 min post ischemia. Cerebral blood flow and metabolism were measured for 2 h postischemia. Delayed treatment with nimodipine ameliorated or reversed the cerebral hypoperfusion that routinely occurs after complete ischemia. In the groups treated at 15 and 30 min, CBF remained above 60 ml min-1 100 g-1. In the group treated at 60 min, there was a progressive decline in CBF to 37 ml min-1 100 g-1. Following treatment with nimodipine, CBF immediately increased and was maintained above 50 ml min-1 100 g-1 for the remainder of the study. Once treatment with nimodipine was begun, CBF was approximately double that of an untreated group. Changes in CBF reflected changes in cerebrovascular resistance. Nimodipine had no effect on cerebral metabolism. Since the postischemic hypoperfusion state is believed to contribute to the ultimate neurologic damage following complete ischemia, treatment with nimodipine, even if delayed up to 60 min, may improve the outcome.

Adenine Nucleotides↗
PubMed1986

Preservation of cerebral metabolites by etomidate during incomplete cerebral ischemia in dogs.

Changes in cerebral high-energy phosphate stores and lactate concentration (as evidence for cerebral protection) were studied in dogs treated with etomidate during incomplete global ischemia, which was of a magnitude insufficient to abolish neuronal synaptic activity (as evidenced by electrical activity on EEG). In six dogs the effects of etomidate (5 mg X kg-1) on the rates of adenosine triphosphate (ATP) and phosphocreatine (PCr) depletion and lactate accumulation during 9 min of oligemic hypotension to 31 mmHg were compared with six untreated dogs. In the dogs treated with etomidate the cerebral energy stores of ATP and PCr and the cerebral energy charge were maintained at higher levels than in the untreated dogs, and the cerebral lactate accumulation was significantly less. This effect of etomidate is similar to that of other anesthetics (thiopental and isoflurane) in this model. The authors conclude that in circumstances of ischemia that are insufficient to abolish neuronal synaptic activity, etomidate may improve tolerance of the brain to ischemia by decreasing cerebral metabolism through its suppression of neuronal synaptic activity.

Adenosine Triphosphate↗
PubMed1985

Cerebral functional, metabolic, and hemodynamic effects of etomidate in dogs.

The effects of a continuous infusion of etomidate on cerebral function, metabolism, and hemodynamics and on the systemic circulation were examined in six dogs. The infusion rate of etomidate was progressively increased at 20-min intervals from 0.02 to 0.4 mg X kg-1 X min-1 for 2 h. Cerebral oxygen consumption (CMRO2) decreased until there was cessation of neuronal function as reflected by the onset of an isoelectric EEG. This occurred during an infusion of 0.3 mg X kg-1 X min-1 etomidate when the animals had received a total of 10.7 mg X kg-1 over 91 min. At this time the CMRO2 was 2.6 ml X min-1 X 100 g-1, 48% of control. Thereafter, despite continued administration of etomidate to a total dose of 21.4 mg X kg-1, CMRO2 did not decrease further. Cerebral blood flow (CBF) decreased in association with a marked increase in cerebrovascular resistance but was independent of changes in CMRO2. CBF decreased precipitously from 145 +/- 23 to 72 +/- 6 ml X min-1 X 100 g-1 during the lowest infusion rate of 0.02 mg X kg-1 X min-1 etomidate and stabilized at 34-36 ml X min-1 X 100 g-1 during an infusion rate of 0.1 mg X kg-1 X min-1. CBF remained at this level despite the continued administration of etomidate and a further decrease in CMRO2. Etomidate produced physiologically minor but statistically significant changes in the systemic hemodynamic variables. Assays of cerebral metabolites taken at the end of the infusion revealed a normal energy state and a very mild but significant increase in cerebral lactate to 1.49 mumol X g-1. We conclude that etomidate is a potent, direct cerebral vasoconstrictor that appears to be independent of its effect on CMRO2 and that the cerebral metabolic effects of etomidate are secondary to its effect on neuronal function, with little if any direct or toxic effects on metabolic pathways.

Anesthesia, Intravenous↗