The present study has defined conditions whereby a reversible form of ischemia-induced ARF can be produced in the dog. Unlike previous studies [9-11] which examined the acute phase of NE-induced ARF, this study demonstrates the feasibility of using the model for the longitudinal study of ARF. Such a model may be useful in studying the pathologic and physiologic changes which occur during different phases of ARF. Perhaps most important, this model should also provide a setting in which treatment measures, either prophylactic or therapeutic for ARF, can be examined.

No abstract

The present study investigated the protective effect of acute volume expansion (25%) with isotonic saline, isotonic mannitol, and hypertonic mannitol in a model of unilateral norepinephrine-induced acute renal failure (ARF). Three hours following a 40-min intrarenal infusion of norepinephrine (NE) (0.75 microgram/kg/min), inulin clearance had fallen from a control value of 54.1 +/- 6.5 to 1.3 +/- 1.3 ml/min in untreated dogs and fell similarly (P = NS) to 3.3 +/- 1.5 ml/min in animals preexpanded with 0.9% saline (0.75 ml/kg/min). In contrast, as compared to the untreated animals, inulin clearance 3 hr post NE infusion was significantly greater in dogs preexpanded with 5% mannitol (9.2 +/- 2.5 ml/min, P less than 0.01), or 20% mannitol (16.6 +/- 3.9 ml/min, P less than 0.01). The protective effects of 5% and 20% mannitol were not statistically different from each other. Recovery of renal excretory function in all groups, expressed as 3-hr post NE inulin clearance, correlated with the magnitude of pre NE solute excretion rate (r = 0.612, P less than 0.001) and osmolar clearance rate (r=0.593, P less than 0.001), but not with pre insult inulin clearance (r = 0.233, P = NS) or renal blood flow (r = 0.249, P = NS). In the presence of a profound fall in inulin clearance, proximal tubular (PT) pressures in untreated dogs 3 hr post NE infusion achieved a value equal to control (26 +/- 11 vs. 25 +/- 2 mm Hg). In contrast, pretreatment with isotonic mannitol produced a rise in PT pressure both before (45 +/- 4 mm Hg, P less than 0.05) and 3 hr post NE infusion (38 +/- 5 mm Hg, P less than 0.05). In all groups of animals, at both 3 and 24 hr post NE, tubular injury was observed but glomerular architecture remained normal by light and electron microscopy. Conclusion. the protective effect of mannitol in this reversible model of ARF did not correlate with inulin clearance, renal blood flow, extracellular fluid (ECF) volume, ECF hypertonicity, or renal histologic changes but did correlate with the solute excretion rate. The increased PT pressures with mannitol both before and after the NE insult could contribute to the protective effect of attenuating any relative intratubular obstruction.

No abstract

Background: Plasma free metanephrines are a more reliable analyte to measure than catecholamines for the biochemical diagnosis of pheochromocytomas. We hypothesized that the long persistence of total (sulfate-conjugated plus free) metanephrines in the blood might have a significant diagnostic value. Methods: We measured plasma concentrations of catecholamines and total metanephrines (sulfate-conjugated plus free forms) by HPLC with amperometric detection, and neuropeptide Y (NPY) by an amplified ELISA in seven patients before and after removal of their pheochromocytomas. The results for catecholamine, total metanephrines, and NPY in each patient were analyzed for up to 120 min, starting from the time of tumor vessel clamping. The persistence of analytes was quantified as the area under the concentration–time curve over 120 min. Results: On the basis of the upper reference limit for each variable, plasma free norepinephrine (NE) and epinephrine (E) concentrations were increased preoperatively in at least one sample in seven and six patients, respectively. Total normetanephrine (NMN) and metanephrine (MN) were increased in all samples in seven and six patients, respectively. NPY was increased 2- to 465-fold. After removal of the tumor, MN and NMN showed a higher average relative increase above the upper limit of the reference interval than NE and E (P = 0.05), whereas NPY was intermediate. The persistence of increased values was significantly shorter for catecholamines than for metanephrines. The half-life estimated by nonlinear regression was 12.3 ± 7.8 min for NPY. Significant correlations were observed among NE, E, NMN, MN, and NPY concentrations, but parent markers (E and MN or NE and NMN) did not appear significantly intercorrelated. Conclusions: A larger increase and a longer persistence of total metanephrines (reflecting predominantly sulfo-conjugated metanephrines) than catecholamines and NPY in plasma may contribute to their greater diagnostic accuracy in pheochromocytoma.

The mechanism whereby an increase in left atrial pressure (LAP) causes a water diuresis in the anesthetized dog remains controversial. In the present study LAP was increased by inflation of an atrial balloon in two groups of animals. In the first group of eight intact dogs, mean LAP was increased from 3.4 to 17.6 mm Hg (P less than 0.001). The rise in LAP was associated with a mean increase in urine flow (V) from 0.70 to 1.29 ml/min (P less than 0.001), a decrease in urinary osmolality (Uosm) from 808 to 490 mOsm/kg of H2O (P less than 0.001) and an increase in free water clearance (CH2O) from -0.684 to -0.200 ml/min (P less than 0.025). This diuresis was associated with a mean decrease in antidiuretic hormone concentrations in plasma as measured by radioimmunoassay from 27.6 to 12.3 pg/ml (P less than 0.02). The changes in the urinary indexes and in the antidiuretic hormone concentrations were reversible and returned to control levels when the LAP was allowed to return to normal. A second group of dogs was acutely hypophysectomized, steroid replaced and given a constant infusion of vasopressin. In these animals, mean LAP was increased from 3.0 to 16.0 mm Hg (P less than 0.001) but no significant change in V (0.49 to 0.56 ml/min), Uosm (878 to 845 mOsm/kg of H2O) or CH2O (-0.750 to -0.620 ml/min) occurred. Cardiac output, renal arterial pressure, glomerular filtration rate and solute excretion were comparable in the two groups. We therefore conclude that suppression of antidiuretic hormone release is the primary mechanism whereby increased LAP causes a water diuresis in the anesthetized dog.

We report on a cirrhotic patient who presented with an aortic valve endocarditis due to Pasteurella multocida. This disease entity is rare and we take this opportunity to review the 6 cases published to date.

The His-Purkinje system of our LQTS patient displayed dynamic properties with a strong increase in refractoriness for short-long sequences and a decrease for long-short sequences that triggered intermittent 2:1 AV blocks.