Angiotensin II restoration of reflex adrenal medullary secretion to anephric dogs is physiologically dose dependent.

Acute nephrectomy seriously impairs hypovolemic adrenal epinephrine (E) release in the anesthetized dog. That systemically delivered angiotensin II totally restores E release to acutely anephric dogs is equally clear, but the dose-response relationship of this angiotensin II effect is not known. Adrenal secretion rates and arterial plasma E, norepinephrine (NE), and dopamine levels were studied in nine groups of mongrel dogs (n = 5 in each group) under pentobarbital anesthesia: 1) resting animals; 2) hemorrhage (25 ml/kg); 3) hemorrhage after acute nephrectomy; 4-7) hemorrhage, acute nephrectomy, plus iv angiotensin II at a) 0.01 ng/kg X min, b) 0.10 ng/kg X min, c) 1.00 ng/kg X min, or d) 10.00 ng/kg X min; 8) no hemorrhage, acute nephrectomy, angiotensin II (10.00 ng/kg X min); and 9) hemorrhage, kidneys intact, iv angiotensin II (10.00 ng/kg X min). Arterial and adrenal blood were sampled during a baseline prehemorrhage period and 15, 30, 60, and 90 min after hemorrhage. We confirm blunting of reflex E release by acute nephrectomy in the anesthetized dog and show that angiotensin II restores E (P less than 0.01), NE (P less than 0.01), and dopamine (P less than 0.01) release in acutely anephric dogs. Aortic plasma E and NE were also restored to normal by angiotensin II (P less than 0.01 for each). Dogs with intact kidneys show a blunted hemorrhage response of arterial plasma E (P less than 0.01), NE (P less than 0.01), and DM (P less than 0.05) to our largest angiotensin II infusion rate (10 ng/kg X min). The study demonstrates that in acutely anephric conditions, angiotensin II support of reflex catecholamine release is sensitively dose dependent to physiological infusion rates of systemic angiotensin II and suggests further that this angiotensin II effect is restrained by the kidneys.

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, Student's test, Fischer's 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)

Primary hyperparathyroidism: four- to eight-year postoperative follow-up demonstrating persistent functional insignificance of microscopic parathyroid hyperplasia and decreased autonomy of parathyroid hormone release.

Thirty-nine patients with primary hyperparathyroidism were studied four to eight years after their initial operation. In six patients, both the pathologist and surgeon agreed on the diagnosis of solitary adenoma; in 16 patients, the surgeon diagnosed solitary adenoma and the pathologist parathyroid hyperplasia (microscopic hyperplasia). In 16 patients, primary chief cell hyperplasia was agreed upon by the pathologist and surgeon. In the 16 patients with microscopic hyperplasia, there have been no long-term recurrences of hypercalcemia, but, in two patients, plasma parathyroid hormone levels are high. Parathyroid hormone--total calcium regression curves demonstrate significant preoperative correlation in solitary adenoma, p less than 0.01, and primary chief cell hyperplasia, p less than 0.05. After operation, significant correlations were not found between parathyroid hormone and total calcium. T-testing slope differences of pre- and postoperative parathyroid hormone--total calcium regression curves demonstrates a significant (p less than 0.01) shift to the right of the microscopic hyperplasia patients after operation, moving them to a broader range of total calcium per picogram parathyroid hormone. We conclude that 1) in primary hyperparathyroidism, positive regulation of total calcium by autonomously released parathyroid hormone exists in patients with solitary adenoma and chief cell hyperplasia; 2) autonomously functioning parathyroid tissue has been removed by operation for solitary adenoma with coexistent microscopic parathyroid hyperplasia. In this four- to eight-year follow-up period, it is clear that microscopic parathyroid hyperplasia is not associated with recurrent hypercalcemia. Two functionally distinct forms of parathyroid suppression are suggested; positively regulated microscopic hyperplasia and negatively regulated pathologically suppressed glands.

Adrenal medullary epinephrine secretion: effects of cortisol alone and combined with aminoglutethimide.

Adrenal E synthesis is thought to require locally high glucocorticoid concentrations to induce the enzyme PNMT for methylation of NE. By suppressing ACTH secretion, exogenous glucocorticoids may limit secondarily adrenal medullary E production. AG, a competitive inhibitor of adrenal steroidogenesis, also may limit adrenal medullary E synthesis. In the present study, three groups of male beagles (mean wt. 9.45 kg) were studied with controlled endotracheal ventilation (98% O2/2% CO2) under Na pentobarbital anesthesia after a 2-week period during which group 1 (N = 4) received no drug, group 2 (N = 5) received C (0.5 mg/kg b.i.d.), and group 3 (N = 4) received C (0.5 mg/kg b.i.d.) and AG (20 mg/kg b.i.d.). Adrenal medullary secretions of E and NE were determined (single isotope radioenzymatic assay) at 15 min intervals over 1 hr basal period and 15 and 30 min following rapid hemorrhage to 50 mm Hg mean arterial pressure. Mean resting adrenal medullary E secretion of group 1 (0.576 +/- 0.181 (1 S.D.) micrograms/min) exceeded that of group 2 (C) (0.150 +/- 0.026 micrograms/min, p < 0.01) and group 3 (C and AG, (0.144 +/- 0.071 micrograms/min, p < 0.01). Maximum E secretion after hemorrhage was higher in group 1 (3.450 +/- 1.990 micrograms/min) than in group 2 (0.649 +/- 0.300 micrograms/min, p < 0.05) and group 3 (0.717 +/- 0.129 micrograms/min, p < 0.05). Highest measured E concentration after hemorrhage was also lower in treated groups (C, p < 0.01) (C and PG p < 0.01). C recipients also had suppressed resting and early reflex (p < 0.01) NE secretion. These results are consistent with the functional importance of the intimate anatomic relationship between the adrenal cortex and medulla. A defect in E-related adrenergic reflexes may occur in patients treated similarly to these experimental groups.

Converting enzyme inhibition augments and competitive inhibition of angiotensin II partially restores reflex adrenal catecholamine release in anephric dogs.

Adrenal epinephrine (E) release after hemorrhage in anesthetized dogs is blunted by acute nephrectomy and restored by angiotensin II infusion. In the present study, we report the effect of converting enzyme inhibition by SQ 20881, a decapeptide, and of competition inhibition of angiotensin II by saralasin (1-Sar-8-Ala-Ang-II) on reflexly stimulated adrenal release of E and norepinephrine (NE) in three groups of acutely anephric dogs. Aortic catheters and adrenal vein to femoral vein Silastic shunts were placed in dogs anesthetized with pentobarbital and mechanically ventilated. Adrenal secretion rates were calculated from adrenal vein to aorta catecholamine concentration differences divided by measured adrenal venous flow. Catecholamine concentrations were determined with trihydroxyindole technique. Blood samples were obtained before and 15, 30, and 60 min after rapid hemorrhage to a stable mean arterial pressure of 50 mm Hg. Saralasin infusion (10 microgram/kg/min) supported adrenal E release in anephric hemorrhaged dogs toward secretion rates comparable to those seen in intact dogs. Anephric SQ 20881 (approximately 0.5 microgram/kg) recipients had delayed (60 min) augmented adrenal E and NE release after hemorrhage. In resting animals not reflexly stimulated by hypovolemia, neither drug provoked adrenal E or NE release. These results suggest an agonist effect of saralasin on reflex adrenal E release and increased responsiveness of the stimulated adrenal medulla under the influence of converting enzyme inhibition.

Cardiac output following adrenomedullary deprivation.

This study was performed to determine whether or not the adrenal medulla supports cardiac output and total peripheral vascular resistance after acute hypovolemia. Two groups of anesthetized dogs were studied. The first group underwent right adrenalectomy and the second, left adrenal denervation in addition. Adrenocortical function, as reflected by compound F and dihydroepiandrosterone determinations, was equally maintained in both groups for 120 minutes after hemorrhage. Arterial plasma concentrations of norepinephrine and epinephrine were low in group 2, p greater than 0.05 to greater 0.01. Cardiac index and peripheral vascular resistance were comparable in both groups before and for two hours after the induction of hypovolemia to a mean arterial pressure of 50 millimeters of mercury. The findings indicate that cardiac output and total peripheral resistance do not require adrenomedullary catecholamine release after acute hypovolemia.

A selective approach to outpatient breast biopsy under local anesthesia.

Outpatient breast biopsy was recommended for women who had a clinically benign, relatively small, accessible breast mass and for a few women with clinical cancer who would not consent to biopsy and possible mastectomy under general anesthesia. Inpatient biopsy under general anesthesia, with possible immediate mastectomy, was recommended for women who had clinical cancer, a large mass or a mass deep within a large breast, and to a few women psychologically unfit for local anesthesia. The incidence of malignancy was 8% in the 153 outpatients and 45% in the 114 inpatients. The incidence of complications between the two groups was not significantly different. The total cost of inpatient biopsy under general anesthesia was over five times higher than that of outpatient biopsy under local anesthesia. Outpatient breast biopsy is a satisfactory approach for appropriately selected patients.