Citations

The effects of severe hypoglycemia on brain pH, cerebral blood flow (CBF), and other physiologic and metabolic parameters were studied in 26 cats subjected to insulin hypoglycemia. Two groups were utilized to compare the effects of anesthesia. The halothane group was composed of 14 animals and the barbiturate group contained 12 animals. Insulin was administered by both the intravenous and intramuscular routes until there was a severe electroencephalographic (EEG) change or until 6 h had elapsed. The cerebral responses to hypoglycemia demonstrated the following: CBF was unaffected by severe hypoglycemia in normotensive animals with or without EEG changes; brain pH was essentially constant in all groups regardless of glucose levels, CBF, or EEG; and the EEG abnormalities corresponded closely to brain glucose levels. Cerebral adenosine triphosphate and phosphocreatine levels were lowest in the animals with isoelectric EEGs. We conclude that CBF and brain pH in the normotensive cat under general anesthesia are relatively unaffected by insulin hypoglycemia despite the presence of severe EEG changes and cerebral energy reserves. The study suggests that the P a co 2 –CBF response curve is not dependent upon the metabolic integrity of cerebral tissue and is mediated by pathways separate from those of autoregulation.

AbstractMinimally invasive techniques have had a marked impact on colorectal surgery despite the limited adoption of such techniques. Patients stay in the hospital a shorter time, experience less pain, and have less chance of developing a wound infection, an incisional hernia, a bowel obstruction, or difficulty becoming pregnant. Training courses have undergone metamorphosis from ad hoc animate courses to highly defined educational opportunities, and fellowships have had to respond to the educational demands of trainees demanding to be exposed to minimally invasive techniques.

Abstract Objective: The aim was to formulate practice guidelines for endocrine evaluation and treatment of pituitary incidentalomas. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails and one in-person meeting. Conclusions: We recommend that patients with a pituitary incidentaloma undergo a complete history and physical examination, laboratory evaluations screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. We recommend that patients with incidentalomas not meeting criteria for surgical removal be followed with clinical assessments, neuroimaging (magnetic resonance imaging at 6 months for macroincidentalomas, 1 yr for a microincidentaloma, and thereafter progressively less frequently if unchanged in size), visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm (6 months and yearly), and endocrine testing for macroincidentalomas (6 months and yearly) after the initial evaluations. We recommend that patients with a pituitary incidentaloma be referred for surgery if they have a visual field deficit; signs of compression by the tumor leading to other visual abnormalities, such as ophthalmoplegia, or neurological compromise due to compression by the lesion; a lesion abutting the optic nerves or chiasm; pituitary apoplexy with visual disturbance; or if the incidentaloma is a hypersecreting tumor other than a prolactinoma.

CBF, as measured by the clearance of 133 Xe or 85 Kr in the pentobarbital-anesthetized cat, displays a monotonic increase as the P a co 2 is elevated over a range of 20–60 mm Hg (slope Xe, 1.65 ± 0.14 ml/100 g/min/mm Hg; slope Kr, 1.40 ± 0.11 ml/100 g/min/mm Hg). Clonidine (20 μg/kg i.v.), a centrally acting, α 2 -preferring agonist, reduced the slope of the P a co 2 -CBF response functions for Xe and Kr by 70 and 64%, respectively. Clonidine reduced normocarbic CBF-Xe by 36%, but had no effect on normocarbic CBF-Kr. ST-91, a polar structural analog of clonidine that does not cross the blood–brain barrier, did not reproduce the effects of clonidine when administered at an equivalent dose. This indicates that the effects of clonidine observed were secondary to its action on central rather than peripheral sites. In addition to the effects on the clearance of CBF markers, clonidine reduced the increased MABP otherwise evoked by elevated P a co 2 . Reduction in the MABP response to P a co 2 did not account for the lowering of CBF during hypercarbia. In separate experiments where MABP was elevated to correspond with the P a co 2 -MABP response observed in the absence of clonidine, a comparable reduction in the slope of the P a co 2 response was also observed. In addition, the pressure autoregulatory response was unaltered after clonidine treatment. These observations suggest that the central action of α 2 -receptors on the CBF-CO 2 response cannot be attributed to an altered perfusion pressure.

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 μg kg −1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 μg 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.

In order to investigate the effects of the calcium entry blocker lidoflazine on neurologic outcome in primates following an episode of global brain ischemia. 12 pigtail monkeys ( Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia, followed by 48 h of intensive care treatment and daily neurologic evaluations for 96 h. The monkeys were randomly assigned to receive, in a blind fashion, either lidoflazine 1.0 mg/kg (n = 6) or inactive lidoflazine solvent (n = 6) at 5 min, 8 h, and 16 h postischemia. One monkey in the lidoflazine group did not meet preestablished protocol criteria and was excluded from data analysis. The remaining monkeys were well matched for age, sex, and other physiologic variables. Neurologic outcome was not significantly different between the lidoflazine- and placebo-treated groups (p > 0.5). No monkey in either group achieved a normal neurologic exam by 96 h postischemia. Three lidoflazine-treated monkeys and two placebo-treated monkeys died prior to the 96-h neurologic evaluation. These deaths were judged to be neurologic in origin. The authors conclude that lidoflazine does not improve neurologic outcome in primates when administered after 17 min of complete cerebral ischemia.

The time course of changes in cortical tissue pH (pHi) and blood flow during cortical seizures in halothane-anesthetized cats was examined. The clearance of the molecular form of umbelliferone (Um) was used to estimate focal cortical blood flow (CBFu), whereas the ratio of the molecular to the ionic form of the molecule was used to concurrently calculate the local pHi. Resting pHi and flow in normocarbic animals was 7.116 ± 0.008 and 46 ± 8 ml/100 g/min, respectively. Respiratory induced alterations of Paco 2 over a range of 20–60 torr revealed a correlated change in pHi from 7.39 ± 0.05 to 7.01 ± 0.03 and a monotonic increase in the rate of Um clearance (slope 0.89 ± 0.13 ml/100 g/min/torr). Focal electrical stimulation of the cortex resulted in a rapid vasodilation (50% dilation = 1–3 s) of pial arterioles and venules and an increase in Um clearance. pHi showed no significant change until around 10 s. The maximum fall in pHi occurred by 30–60 s (6.85 ± 0.054). Longer intervals of stimulation (10 min) resulted in no further decline in pHi, but upon cessation of stimulation, pHi remained acidotic for poststimulation periods up to 10 min, with a mild but statistically significant acidosis being observed at 20 min. The absolute decline in pH observed following stimulation appeared to be closely regulated, as comparable levels following stimulation were observed during hypocarbia and hypercarbia. These observations thus suggest that pHi regulation during intense cortical activation may be considered in three phases: (1) following the onset of activity, an initial acute regulation of pHi at control levels; (2) an intracellular acidosis of around 6.8, which is closely regulated and which can be readily reversed upon termination of stimulation; and (3) during continued stimulation, a change in state where in spite of no further change in pHi, the ability of the cortex to return to control pHi appears to be significantly impaired.

In chloralose-urethanized cats, vasoactive intestinal peptide (VIP), applied by superfusion in steady-state concentration (10 −10 –10 −6 M) onto cortical vessels in situ resulted in a rapid concentration-dependent vasodilatation in vessels that were mildly constricted by prostaglandin F 2α (PGF 2α ) (5 × 10 −5 M) or hypocarbia (P a CO 2 = 26). The maximum dilatation produced by VIP (10 −6 M) was about 60% over baseline in pial arteries and 40% in pial veins. Blockade of local neuronal activity with tetrodotoxin (TTX) (10 −5 M) had no effect on the VIP-evoked dilation of pial vessels. Activation of the cortex by either direct electrical stimulation or indirectly by stimulation of the mesencephalic reticular formation (MRF) resulted in a rapid dilatation of pial arterioles and venules. The vasodilatory effects of VIP and of cortical activation via direct cortical stimulation were not blocked by phentolamine (10 −4 M), propranolol (10 −4 M), atropine (10 −4 M), or naloxone (10 −4 M), indicating that the stimulated vasodilatation was not mediated by adrenergic, cholinergic, or opiate receptors. The dilatory effects of MRF, but not direct cortical stimulation, were not blocked by TTX. VIP antiserum (1:25) preincubated in cortical cups had no effect on resting vessel diameter, but resulted in a significant, though subtotal, reduction in the vasodilatation elicited by direct cortical and MRF stimulation. Normal rabbit sera or VIP antiserum preincubated with saturating amounts of VIP were ineffective. In similar experiments, pial arteriolar and venular dilation evoked by hypercarbia was not attenuated by cortically applied VIP antisera. These observations suggest that pial dilation evoked by local increases in neuronal activity may be mediated in part by the local release of VIP from intrinsic neurons. Such a substrate would define a close obligatory coupling between local neuronal activation and local perfusion, such that nutritive flow could be enhanced prior to the onset of any metabolic deficit.

Nimodipine is known to improve postischemic cerebral blood flow (CBF) and neurologic outcome in experimental animals. Whether or not the two observations are related is unknown. This study searched for a possible improved rate of brain metabolic recovery in animals treated with nimodipine postischemia. Complete cerebral ischemia was produced for 11 min in 16 dogs, followed by reperfusion for 70 min. Prior to ischemia, glucose was administered (0.75 g · kg −1 ) in 12 dogs. Half of the glucose-treated dogs were given i.v. nimodipine, beginning 5 min postischemia (10 μg · kg −1 bolus followed by 1 μg · kg −1 · min −1 ). The other half were given only saline postischemia. The remaining four dogs were given no glucose and received saline only postischemia. In all dogs, serial brain biopsies were taken at 2, 20, 40, and 70 min postischemia. In 5 dogs, the integrity of the blood–brain barrier (BBB) was tested by injection of Evans blue dye and postmortem examination of the brains. Brain biopsies were assayed for concentrations of phosphocreatine, ATP, ADP, AMP, glucose, lactate, and pyruvate. In all dogs, there was rapid restoration of a normal brain energy state following reperfusion. Brain lactate had returned to near normal in all dogs by 70 min postischemia, and the rate of lactate depletion was not different between groups. The integrity of the BBB was only minimally affected. A portion of the brain lactate was converted to pyruvate rather than crossing the BBB. If lactate is a valid marker of the washout of metabolic products postischemia, there is no apparent benefit resulting from a nimodipine-induced increase in CBF during the initial 70 min following ischemia.