Changes in the electroencephalogram in acute uremia. Effects of parathyroid hormone and brain electrolytes.

Studies were carried out in order to evaluate the effects of changes in brain calcium and the influence of parathyroidectomy and administration of parathyroid extract on the electroencephalogram (EEG) of normal and uremic dogs. Manual analysis of frequency and power distribution of the EEG in uremic dogs revealed a significant increase in both the percentage distribution and the area or power occupied by frequencies below 5 Hz. In addition, high amplitude bursts of delta activity were apparent in the uremic dog. These changes were largely prevented by parathyroidectomy before the induction of uremia, but the administration of parathyroid extract to either normal dogs, or to previously parathyroidectomized uremic dogs, induced EEG changes similar to those noted in uremic animals with intact parathyroid glands. In all groups of animals which showed EEG changes, brain content of calcium was significantly higher than in either normal dogs or previously parathyroidectomized uremic dogs. Changes in arterial pH and bicarbonate, or in the concentrations of Na+, K+, urea, or creatinine in plasma or cerebrospinal fluid were similar in uremic animals with intact parthyroid glands and in previously parathyroidectomized uremia dogs. The results indicate that the EEG changes found in dogs with acute renal failure require the presence of excess parathyroid hormone in blood, and they may be related to the observed changes in brain content of calcium.

Lactic acidosis: an experimental model.

A model of spontaneous lactic acidosis was developed in alloxan diabetic rabbits by infusing intravenously beta-hydroxybutyric acid followed by a continuous infusion of NaHCO3. In half of the animals, the arterial lactate/pyruvate ratio rose from 2.5 mM/0.19mM to 20.4 mM/0.28 mM, and arterial pH fell to 7.16. In animals with lactic acidosis, the calculated ratio in blood of NAD/NADH was 1437 +/- 230, versus a normal value of 6754 +/- 1250. Both arterial PO2 and blood pressure were normal. Continued infusion of NaHCO3 led to increased blood lactate levels, with cardiorespiratory arrest in 36% of animals. Lactic acidosis did not develop in normal rabbits who were similarly treated. It is concluded that spontaneous lactic acidosis can be produced in diabetic, but not in normal, rabbits by infusion of beta-hydroxybutric acid followed by infusion of NaHCO3.

Intracellular pH of brain: alterations in acute respiratory acidosis and alkalosis.

To evaluate the metabolic adaptations of the brain to acute respiratory acid-base disturbances, a method was developed to measure intracellular pH (pHi) in the brain of dogs under conditions in which arterial pH is rapidly altered. Brain pHi was determined by measuring the distribution of 14C-labeled dimethadione (DMO) in brain relative to cortical CSF. Brain extracellular space (ECS) was evaluated as the 35SO4 = space relative to cortical CSF, and arterial Po2 was maintained at 82-110 mmHg. In normal dogs, brain (cerebral cortex) pHi was 7.05, and after 1 h of hypercapnia (arterial pH = 7.07) it fell to 6.93. However, after 3 h with arterial Pco2 maintained at 85 mmHg brain pHi was normal (7.06), and during this time brain bicarbonate had risen from 11.3 to 24.4 meq/kg H2O. These changes were not prevented by intravenous doses of acetazolamide,

The effect of chronic furosemide administration on urinary calcium excretion and calcium balance in growing rats.

The study was designed to determine the calciuretic effect of furosemide and its impact upon calcium balance during chronic (25 days) furosemide administration to growing rats. Experiments were performed on 18 six-wk-old rats. Nine animals received furosemide, and 9 served as controls. The administration of furosemide in a dose of 40 mg resulted in a significant increase in calcium excretion in the treated group; urinary calcium excretion almost doubled that of the controls during the first 24-hr collection (3.74 +/- 0.44 mg in the treated animals compared with 1.90 +/- 0.15 mg in the controls; P less than 0.05). The average daily urinary calcium excretion during each of four subsequent 6-day periods remained approximately three-fold higher in animals which received furosemide compared with controls (P less than 0.001 for each 6-day period). The furosemide-induced increase in urinary calcium excretion did not diminish with time. Sodium excretion did not significantly increase either acutely or chronically in response to furosemide. Daily urinary volume increased approximately 40 to 60% in the furosemide-treated group compared with that of the controls (P less than 0.001). The cumulative calcium balance in the control group exceeded by 7% that of the furosemide-treated animals [2696.3 +/- 20.8 mg versus 2518.6 +/- 20.1 mg (P less than .001]. The findings indicate that distal nephron compensatory mechanisms effecting sodium conservation following furosemide do not result in similar conservation of calcium. Calcium balance may be deleteriously affected.