John F. Seaton

Awake epidural anesthesia is associated with improved natural killer cell cytotoxicity and a reduced stress response

BACKGROUND Laparotomy under general anesthesia is associated with depressed natural killer cell cytotoxicity (NKCC) and compromised clearance of tumor cells. We tested the hypothesis that awake epidural anesthesia (AEA) improves NKCC compared to conventional general endotracheal anesthesia (GEA). PATIENTS AND METHODS Preoperative, perioperative, and postoperative (day 3) NKCC, plasma epinephrine, norepinephrine, cortisol levels, and 24-hour urinary cortisol levels were measured in 20 patients undergoing open colectomy under either AEA or GEA. RESULTS Preoperative and postoperative measurements were not significantly different in the two groups. Patients receiving GEA had a significant reduction in NKCC from 36% +/- 4% preoperatively to 22% +/- 4% perioperatively (P = 0.02). Patients receiving AEA had no significant change in NKCC. Perioperative plasma epinephrine and cortisol levels were higher with GEA than AEA. The perioperative 24-hour urinary cortisol excretion values were significantly higher in the group receiving GEA, suggesting a greater stress hormone response in this group compared to AEA patients. CONCLUSIONS Compared to GEA, AEA appears to preserve perioperative NKCC. This effect may be related to an attenuated stress hormone response associated with AEA. Cancer patients may have improved killing of embolized tumor cells during surgery performed under AEA.

Localization of central prostaglandin E2 antisecretory effects

Intracerebroventricular prostaglandin E2 (PGE2) inhibits stimulated gastric acid secretion; however, the central site of action is unknown. Specific PGE2 binding sites have been localized to the ventromedial hypothalamic nucleus and central amygdala (A). The nuclear accumbens has been shown to play a role in central neurotensin-induced antisecretory effects. These studies tested the hypothesis that microinjections of PGE2 into the ventromedial hypothalamic nucleus, central amygdala, and nuclear accumbens inhibit stimulated gastric acid secretion. The hippocampus served as a cerebral control region. Two days before the experiments, metal cannulas were stereotaxically positioned bilaterally into specific areas of the brain, and metal gastric cannulas were operatively implanted, under nembutal anesthesia, in male 250-g Sprague-Dawley rats. On the experimental day, the rats, fasted for 14 hours, were given saline or PGE2 (0.1-1.0 micrograms in 0.2 microL/side) through the central cannulas 10 minutes before administering pentagastrin (40 micrograms/kg SC). Gastric secretion was measured at 30-minute intervals and expressed as acid output, micromoles per hour. Acid output (mean +/- SE) in control animals was 161 +/- 14 mumol/h. Prostaglandin E2 administration at doses of 0.10, 0.50, and 1.0 micrograms/side (a) into ventromedial hypothalamic nucleus reduced acid output to 53 +/- 11,* 36 +/- 10,* and 27 +/- 11* mumol/h regularly; (b) into NACB reduced acid output to 157 +/- 36, 60 +/- 12,* and 38 +/- 12* mumol/h; and (c) into A reduced acid output to 144 +/- 31, 141 +/- 26, and 90 +/- 19* mumol/h, respectively (*P less than 0.05 by Neuman-Keuls test). Prostaglandin E2 (0.50 micrograms/side) administration into hippocampus had no significant effect on acid output (134 +/- 28 mumol/h). Although central PGE2 administration was associated with hyperthermia, this occurred at lower doses than those required to inhibit acid secretion. Prostaglandin E2 administration into specific brain areas known to have PGE2 receptors, the central amygdala and ventromedial hypothalamic nucleus, and into nuclear accumbens inhibits stimulated gastric acid secretion. These observations suggest that PGE2 may have a physiological role in the central control of gastric acid secretion.

Malignant catecholamine-secreting carotid body paraganglioma.

The second known case of a malignant catecholamine-secreting (DA)-secreting carotid body paraganglioma is presented. Dopamine synthesis and secretion can be increased in malignant tumors derived from neural crest cells. Whether this is true, in addition, for extra-adrenal paragangliomas is not yet clear. Malignant paragangliomas of the carotid body and larynx, although rare, frequently have been accompanied by increased catecholamine secretion. Malignant catecholamine-secreting carotid body paragangliomas are best treated by composite resection (internal carotid artery and neck dissection), with special attention being given to measures preventing severe hypertension and arrhythmias in the perioperative period.

HPLC for urinary catecholamines and metanephrines with alpha-methyldopa

In five healthy selected volunteers with normal blood pressure and one pheochromocytoma patient, high performance liquid chromatography (HPLC) has been evaluated, with electrochemical detection for quantitation of urinary catecholamines and metanephrines during administration of the antihypertensive, alpha-methyldopa. The clinical usefulness of HPLC is compared with that of the conventional assay method--the trihydroxyindole (THI)-fluorometric procedure. The THI fluorometric method is known to suffer from true false-positive interference as a result of its inability to differentiate between alpha-methyldopa, its primary metabolic derivatives, and the structurally similar endogenous catecholamines. It is shown that the HPLC separation methodology yields accurate, reproducible results devoid of interference from the presence of alpha-methyldopa. Free urinary excretion rates of epinephrine, norepinephrine, and dopamine were elevated by alpha-methyldopa, P less than 0.001, for epinephrine, norepinephrine, and dopamine when measured by the trihydroxyindole technique but not with high performance liquid chromatography. With alpha-methyldopa treatment, urinary normetanephrine excretion rates were slightly increased, P less than 0.05, by fluorometric analysis and slightly decreased. P less than 0.05, when measured by HPLC. Of added interest, the formation of the normetanephrine analog of alpha-methyldopa, previously undetected, is suggested. Slightly elevated metanephrine levels are seen by the THI-fluorometric method in the presence of alpha-methyl metanephrines. Establishing that the HPLC assay procedure is suitable for clinical diagnosis of pheochromocytoma, despite the presence of alpha-methyldopa, makes it unnecessary to discontinue use of this antihypertensive in screening for pheochromocytoma.

Site-dependent central effects of aldosterone in rats

A relationship between the subcommissural organ (SCO) and the adrenal glands has long been suspected. This report provides further information about the effects of a continuous D-aldosterone infusion into the SCO area of conscious, adult male Sprague-Dawley rats. A 6-day aldosterone infusion (5 ng/h) increased urinary sodium excretion, decreased adrenal medullary cross-sectional area, elevated adrenal corticosterone content and terminal plasma epinephrine concentration. Mineralocorticoid infusions directly into a lateral cerebral ventricle did not affect these parameters but, unlike SCO area infusions, decreased consummatory behavior. Infusions of tritiated aldosterone into the SCO area revealed that radioactivity was mainly confined to dorsomedial portions of the brain near the SCO, whereas the pineal body contained only background radioactivity. The data support the concept that the SCO area interacts with physiological systems related to both the adrenal cortex and medulla.

Monoamine oxidase B inhibition reduces gastric mucosal blood flow, basal acid secretion, and cold water restraint-induced gastric mucosal injury in rats

Inhibition of monoamine oxidase B (MAO B) by selective inhibitors pargyline andl-deprenyl increases dopamine (DA) and norepinephrine (NE) concentrations in nucleus accumbens (NACB) and is associated with reduction in cold water restraint-induced gastric mucosal injury, inhibition of basal gastric acid output, and regional gastric mucosal blood flow. Similar effects were not observed with administration of MAO A inhibitors. These observations suggest that activation of central dopamine and norepinephrine receptors, particularly in NACB, are involved in the control of gastric mucosal function.

Renal modulation of electrically stimulated adrenal medullary secretion

In acutely anephric dogs, depressed reflex adrenal medullary secretion (AMS) may be related to low plasma angiotensin. Either local (adrenal medulla) or central nervous system mechanisms are responsible. Local influences of acute bilateral nephrectomy on AMS were evaluated after left splanchnic nerve section. Two groups of five healthy, fasted mongrel dogs (16-20 kg) were prepared (Na pentobarbital iv anesthesia, 98% O2/2% CO2, Harvard volume ventilator) at celiotomy with blood pressure and sampling catheters per femoral arteriotomies and left adrenal-femoral venous T-shaped Silastic shunt. Group 2 dogs had acute bilateral nephrectomy. The acutely divided distal left splanchnic nerve was arranged for electrical stimulation (Grass, bipolar nerve stimulator, 1 0 V, 1-msec delay, 10 Hz, 10-msec square wave). Heparin anticoagulation was maintained and arterial pH monitored. Simultaneous adrenal vein, aortic blood sampling, and adrenal blood flow (F) determinations followed 10-min periods of alternating electrical stimulation and nerve rest. AMS for epinephrine (E) and norepinephrine (NE) was calculated [E and NE plasma concentration (single isotope radioenzymatic technique) differences of adrenal vein minus aorta multiplied by F]. Results were grouped, analyzed for variance, and compared (Wilcoxon unpaired rank sum, Students test, Fischers tables, ANOVA). Low aortic E, NE concentrations confirmed absent systemic adrenergic stimulation. The AMS ratio of NE:E was low in the anephric group. At the first stimulation interval NE:E was 0.28 +/- 0.14 (1 SD) in renal intact dogs vs 0.11 +/- 0.04 in anephric dogs, P less than 0.05. At rest NE:E was 0.33 +/- 0.12 in group 1 vs 0.17 +/- 0.02 in group 2 dogs, P less than 0.02. Plasma NE was also low in the anephric group (289 mg/liter +/- 126 (1 SD) vs 612 +/- 189, P = 0.033, resting).(ABSTRACT TRUNCATED AT 250 WORDS)