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The effect on renal function of a 210-min infusion of PGA1 into the aorta of 10 conscious beagle dogs has been investigated. In the sodium-replete group, PGA1 caused an increase in the glomerular filtration rate (GFR) (24%), renal blood flow (17%) and sodium excretion (20%). By contrast, in the sodium-depleted group, PGA1 caused a considerable reduction of GFR (25%) and sodium excretion (51%). In this group, baseline renal blood flow was lower, and there was no further reduction during PGA1 infusion. Fractional sodium excretion was unchanged in the sodium-replete dogs, but was reduced in the sodium-deplete state. Plasma renin activity was markedly elevated and further increased in the sodium-deplete group, but it was nearly unchanged in the sodium-replete group. This difference in renal response to exogenous PGA1 might be due to interaction with the renin-angiotensin system, which was markedly stimulated by sodium depletion and additionally by prostaglandin infusion.

As a renal function declines in patients and experimental animals with chronic renal disease, potassium homeostasis is maintained by a progressive increase in potassium secretion by the surviving nephrons, a phenomenon known as potassium adaptation. To determine the nephron site and the underlying mechanisms responsible for this phenomenon, studies were performed on normal and 75% nephrectomized rabbits maintained on normal or high-potassium diets. Cortical collecting tubules (CCT) were dissected from the normal and remnant kidneys and perfused in vitro in an artificial solution. In normal CCT mean (+/- SE) net K secretion, JK, (peq/cm per s) was 1.26 +/- 0.43 (normal diet) and 3.27 +/- 0.66 (high-K diet). In uremic CCT, JK was 3.55 +/- 0.60 (normal diet) and 6.83 +/- 0.58 (high-K diet). By reducing the dietary intake of potassium in proportion to the reduction of renal mass in these uremic animals, the adaptation in K secretion was prevented (JK: 1.22 +/- 0.40). Transepithelial potential difference was similar in CCT from normal and uremic animals on a normal diet despite the fact that JK was significantly greater in the latter group. However, in both normal and uremic CCT, the increase in JK caused by potassium loading was associated with an increase in luminal negativity. Uremic CCT underwent significant compensatory hypertrophy regardless of the dietary intake or potassium secretory rates. Plasma aldosterone levels were elevated only in the uremic-high potassium rabbits suggesting that a mineralocorticoid effect on the CCT may be exaggerated when potassium loading is superimposed upon decreased excretory capacity. The activity of Na-K ATPase was comparable in normal and uremic CCT from rabbits on either normal or high-K diets indicating that potassium adaptation may occur independently of changes in the activity of this enzyme. Intracellular potassium content measured chemically and by 42K exchange, was not significantly altered in either normal or uremic CCT when dietary potassium intake was increased, despite the fact the JK was increased under these circumstances. These data indicate that the CCT is an important site of potassium adaptation in the surviving nephrons of animals with reduced renal mass. This adaptation is an intrinsic property of the CCT and is expressed in the absence of a uremic milieu. Potassium adaptation by the uremic CCT is not fixed according to the degree of compensatory hypertrophy but varies according to the excretory requirements of the animal. Transepithelial potential difference and circulating aldosterone levels contribute to the adaptation but neither factor can entirely account for the phenomenon. Potassium adaptation by the CCT occurs in the absence of changes in Na-K ATPase activity and intracellular potassium content.

The influence of low-sodium dialysate (126 mmol/l) on plasma levels of prostaglandin E2 (PGE2) and PGF2α, plasma renin activity (PRA) and arterial blood pressure was investigated in 16 patients on maintenance hemodialysis. PGE2 rose more than tenfold and there was a significant increase in PGF2α and PRA. Mean arterial pressure dropped by 30 mm Hg causing discomfort in several patients. By contrast, conventional hemodialysis against 140 mmol/l of sodium was followed by less pronounced changes in plasma prostaglandins, and reduction of blood pressure was moderate (13 mm Hg). It is suggested that vasodilating prostaglandins may contribute to dialysis hypotension. Their origin may not be confined to the kidneys but rather extend to the lungs and circulating blood cells. The in vitro generation of prostaglandins was demonstrated when donor blood was circulated in an extracorporeal dialysis system.

Implementation of the principles of IEEE 384 and Regulatory Guide 1.75 can help to assure that independence between redundant Class 1E systems is achieved. But designers should not lose sight of the several ways in which this goal can be accomplished. In selecting which method to use in a particular circuit or system, the reliability, maintainability, and cost of each method should be considered along with the independence achieved. The exclusive use of either isolation, separation, or analysis in the multitude of power and instrumentation circuits in a nuclear plant can result in a costly and less-than-optimum design. In determining the most practical approach for implementing IEEE 384 and Regulatory Guide 1.75 the following points should be considered: 1. Initial efforts should be directed toward proper classification of all circuits as Class 1E, Associated, or non-1E. The safety and non-safety function should be evaluated. 2. The use of analysis should be put in proper perspective. It can be used to establish credible faults and criteria for isolation/ separation; it cannot replace the need for proper isolation/ separation. 3. The method of isolating or separating circuits is best determined on a case-by-case basis as opposed to a blind following of blanket criteria. Frequently the best choices are either to separate redundant channel associated circuits or to utilize existing isolating features as the "qualified isolator". 4. Isolation devices, where used, should be specified keeping in mind the intended purpose of the device.

The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n=5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n=6, posttreatment) an intra-aortic injection of diltizem (5 µg·min−1·kg−1) beginning at the end of ischemia until the 7th day. Group C (n=7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149±16 (preischemic) to 129±29 ml·min−1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29±15% (group B,P 0.05) and 14±13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group. In group C, the glomerular filtration rate was significantly less reduced than in group A (34±1.8 preischemically to 17±5.4 on day 1,P 0.05 and 20±4.1 ml·min−1 on day 7,P 0.05). Plasma renin activity increased in both diltiazem groups, more pronounced so in group B (from 3.7±1.0 on day 1 to 16.2±7.9 ng ATI·ml−1·h−1 on day 7,P 0.05). In contrast to groups A and B, the increase in fractional sodium excretion was less pronounced in group C. Likewise, the decrease in free water-reabsorption was less marked than in groups A or B. It was apparent that diltiazem, when administered pre- and post-ischemically, preserved glomerular filtration rate and renal blood flow. When diltizem was given solely postischemically there was an improvement in renal blood flow, but no significant influence on glomerular filtration rate. We therefore conclude that mainly tubular factors, in addition to the attenuation of postischemic vasoconstriction, are involved in the protective effect of diltiazem on postischemic acute renal failure in conscious dogs.

In a nineteen-year-old male in whom severe and protracted hypertension developed after a successful renal transplantation, the removal of the diseased kidneys resulted in restoration of normal blood pressure. Prenephrectomy blood samples obtained from the venous drainage of all three renal veins demonstrated no evidence for excessive renin secretion, nor was a significant difference in renin activity found between any two kidneys. It is postulated that the patient may be a clinical variant of the experimental form of renal hypertension with normoreninemia. Alternatively, the remnant kidneys may be implicated to produce a nonrenin pressor substance.

Gastrointestinal protein loss was studied by intravenous application of 51Cr-albumin and the measurement of fecal excretion of 51Cr. As compared to controls, fecal excretion of 51Cr was largely increased in 28 patients with nephrotic syndrome due to glomerular disease and in 11 patients with hypoproteinemia in the course of different gastrointestinal disorders. It was not increased in nephrotic patients without primary glomerular disease and in renal insufficiency without nephrotic syndrome. Controversial data of the literature are discussed with regard to different methods and patient groups.

Low frequency fluctuations (five to 10/min) in blood pressure, that is vasomotor waves, were recorded in the erect position in 18 patients operated upon for an isolated aortic coarctation six to eight and a half years previously, and compared with vasomotor waves in six age matched normotensive controls with respect to frequency and amplitude. The investigation was carried out by simultaneous intra-arterial blood pressure radiotelemetry recordings from the brachial and femoral arteries in all but four of the controls. While the vasomotor wave frequency and blood pressure response to the erect posture was of the same order in the two groups, a highly significant difference was found with the amplitude of the vasomotor waves, being higher in the controls than in the patients. Furthermore, the results seem to indicate a negative correlation between age at the time of surgical repair and vasomotor wave activity (mmHg/min). It is suggested that the reduced vasmotor wave activity is brought about mainly by a disturbed input (from the baroreceptors) to the brainstem oscillator(s), caused by a combination of preoperative hypertension and prolonged exposure to high blood pressure.

Most of the 52 patients on maintenance dialysis investigated in this study suffered from arterial hypertension in spite of efforts to reduce ‘dry weight’. In this situation we found that the majority

The effect of a continuous intra-aortal infusion of prostaglandin E2 (PGE2) (0.03 µg· min-1 • kg-1) on the course of postischemic renal failure (180 min cessation of blood flow by inflation of a pneumatic cuff) has been investigated in 11 conscious sodium-replete dogs. The glomerular filtration rate (51Cr-EDTA; endogenous creatinine clearance) was less decreased in the PGE2 group (group B, n = 6) than in the control group (group A, n = 5; 13 ml·min-1 vs. 22 ml min-1; p < 0.05). Renal blood flow (electromagnetic flow probe) was markedly lower in the control group (82 ml •min-1) than in the PGE2 group (130 ml • min-1; p < 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+ 277%) was abolished in the PGE2 group (-20%) (ρ < 0.05). Nitrogen retention was also markedly improved. Plasma renin activity, which was markedly raised initially (25.8 ng angiotensin I·ml-1 h-1) was not significantly further increased during the subsequent 7 days. Urinary excretion of PGE2 was diminished in the control group and elevated following PGE2 infusion. It is suggested that the beneficial effects of PGE2 are mediated by preservation of renal perfusion. Additional effects of prostanoids on the ultrafiltration coefficient (KF) and cytoprotection by reduction of intracellular calcium accumulation must also be taken into consideration.

Eicosanoids are potent substances released from blood cells after contact with foreign materials. Eicosanoid generation, in addition to complement fragment formation, may be a valuable indicator of the biocompatibility of dialyzer membranes. In the present in vitro study, eicosanoid generation induced by several different flat dialyzer membranes [polyacrylonitrile (PAN), cuprammonium cellulose (CC), and polycarbonate (PC)] was evaluated and compared using blood from non-uremic healthy volunteers. Generation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was greatest with PC followed by PAN and CC. The formation of C3a des arg with PAN was less than with either CC or PC. Our results suggest that dialyzer membranes affect complement activation and eicosanoid generation differently; biocompatibility as expressed by a low level of complement fragment formation does not necessarily translate into biocompatibility when considering eicosanoid generation.

Two double-blind studies were performed in allergic subjects with bronchial asthma to evaluate the bronchodilator effect and antiallergic protection of oxitropium bromide (OTB), a new antiallergic dru

We compared our in-house reference extract (RE) and a production extract (PE) with the international reference preparation (IRP) of International Union of Immunological Societies of timothy-grass pollen, using various biochemical and immunochemical methods. Furthermore, we compared the IgE composition of our in-house grass-pollen serum pool (West Germany) with the serum pool recommended by the World Health Organization, using the RE for crossed radioimmunoelectrophoresis (CRIE). Our extracts (RE and PE) were nearly comparable with the IRP. Only by CRIE one more allergen could be detected in RE and PE than in IRP and in another extract purchased from an American company. This finding may depend on the region where the source materials were harvested and which source materials were used for the preparation of the extracts. Furthermore, by high-performance liquid chromatography in the low-molecular-weight range, two distinct peaks could be detected in the nondiafiltered IRP, which were detected in the diafiltered RE and PE as traces only. The IgE composition of our in-house grass-pollen serum pool was comparable with the serum pool recommended by the World Health Organization, as detected by CRIE using RE.

Two healthy young males on a constant normal sodium diet (135 mM/day) were infused for 132 h with 3 ng/kg/min of angiotensin II. Plasma angiotensin II levels were therby raised to the range of moderate sodium depletion. Plasma aldosterone and the urinary excretion rate of aldosterone-18-glucuronide were markedly increased during the whole infusion period and returned to control levels after the infusion was stopped. A slight tendency of aldosterone secretion to decrease towards the end of infusion was probably due to sodium retention (appr. 200 mM and 350 mM respectively) and to a fall in plasma potassium by approximately 0.5 mM/1. Plasma aldosterone during infusion, maintained circadian variations similar to those of cortisol. Plasma cortisol patterns were unaffected by angiotensin II. Blood pressure increased gradually during angiotensin II infusion, reflecting changes in sodium balance. The results, differing from those of studies in dog and sheep, support the assumption that angiotensin II is an important regulator of aldosterone secretion in man rather than a merely permissive factor.

6 gesunde untrainierte Normalpersonen im Alter von 22–35 Jahren wurden 4 Wochen lang taglich, auser sonntags, mit einer stufenweise bis zum Maximum gesteigerten Belastung trainiert. Taglich wurde die Sauerstoffaufnahme, das Atemminutenvolumen und die Herzfrequenz bei 100 W steady state Belastung und bei maximaler Belastung registriert. Zweimal wochentlich wurde 3 min nach Belastung das pH und die ubrigen Werte des Saure-Basen-Haushaltes bestimmt. Die maximale Sauerstoffaufnahme nahm im Verlauf des Trainings um 14,9% zu, das maximale Atemminutenvolumen um 17,5%. Die maximale Herzfrequenz nahm um 3,2% ab, der pH-Wert 3 min nach Beendigung der Belastung nahm aus metabolischer Ursache um 0,09 ab.

An effort to examine certain aspects of the adaptation in potassium excretion associated with nephron reduction was made in dogs with unilateral remnant kidneys. A constant intake of potassium was maintained by tube feeding and studies were performed before and after removal of the intact control kidney. The removal of the intact kidney created the need for the remaining nephrons of the remnant kidney to increase their rate of potassium excretion markedly. Sodium intake was held constant either at a normal or a low level. Mineralocorticoid hormone activity was maintained either at a high level by the administration of 0.2 mg 9-alpha-fluorohydrocortisone daily or at a low level by performing bilateral adrenalectomy and administering a minimal maintenance dose of deoxycorticosterone acetate (DOCA) and cortisol. Potassium excretion per nephron increased strikingly within 18 hr of contralateral nephrectomy and by 7 days, excretion rates were 600% of control values for the remnant kidney. More potassium was excreted in the first 5 hr after administration of a test dose of potassium by the remnant kidney alone in the postnephrectomy state than by both the remnant and intact kidneys in the prenephrectomy state. 24 hr excretion of potassium by the remnant kidney postnephrectomy averaged 92% of the administered load of potassium. The adaptation in potassium excretion was independent of the concurrent rate of sodium excretion and of mineralocorticoid hormone activity and persisted during constriction of the renal artery, a stimulus which presumably decreased distal delivery of sodium. The adaptation and the continued modulation of potassium excretion could not be explained adequately by an increase in impermeant anion excretion per nephron. Finally, known changes in hydrogen ion excretion per nephron associated with nephron reduction are in a direction opposite to those which would explain the acquired kaliuresis per nephron.

Bei hypertonen Ratten (9 Wochen nach Klammerung einer Nierenarterie) und normotonen Kontrolltieren wurden der statische Druck, das Erythrozyten- und Plasmavolumen und der zentralvenose Druck bestimmt.

Fur die Entfernung von Oberflachenverunreinigungen von Metallen stehen heute verschiedenartige Behandlungsmethoden zur Verfugung, die kurz umrissen wurden. Die chemische Reinigung durfte an Bedeutung gewinne, und zwar um so mehr, je allgemeiner die Bedeutung der sauberen Metalloberflache fur den weiteren Einsatz erkannt wird. In immer hoherem Mase wird der sauren Beizung der Vorzug gegeben und trotz der bisher erreichten uberraschenden Ergebnisse durfte bei systematischer Bearbeitung der Schutzeffekt noch wesentlich umfassender gestaltet werden konnen.

A study of the mechanisms governing the high rate of sodium excretion per nephron characteristic of patients with chronic renal disease has been made in dogs. A "remnant kidney" was produced by 85% infarction of the left kidney while the right kidney was left intact. A bladder-splitting procedure allowed simultaneous measurement of glomerular filtration rate and the rate of sodium excretion by each kidney. The animals were fed a constant known amount of sodium chloride and 0.1 mg of 9 alpha-fluorohydrocortisone twice daily throughout the study. In a group of dogs fed 3 or 5 g of salt per day, sodium excretion by the remnant kidney averaged 6.5 muEq/min while the intact kidney was present and 53.7 muEq/min when the animals became uremic after the intact kidney was removed. The increased sodium excretion per nephron by the remnant organ often occurred within 18 hr after contralateral nephrectomy and persisted despite experimentally induced acute reductions in the glomerular filtration rate to below prenephrectomy levels. A second group of animals studied in the same manner but receiving 1 g of salt per day or less failed to develop a natriuresis after contralateral nephrectomy despite high grade uremia. Thus an increased impermeable solute load per nephron was not a regulatory factor in the production of the natriuresis. The increased rate of sodium excretion per nephron in uremia resembles that after saline loading in that it may occur without an increase in glomerular filtration rate or a reduction in mineralocorticoid stimulation. It follows that an additional factor or factors must be involved in the genesis of the natriuresis. In contrast to the natriuresis that is seen in normal animals subjected to saline loading, these uremic animals were found not to have a detectable increase in extracellular fluid volume or blood volume in the presence of high fractional sodium excretion rates. Sodium excretion in response to a small salt load by the remnant organ in uremia was 30% greater than the response of both kidneys in the preuremic state despite a markedly reduced total GFR. These data are consistent with the view that the volume control mechanism becomes more responsive in uremia.

The influence of uremia on fractional sodium reabsorption by the proximal tubule. Micropuncture and clearance studies were performed on four groups of rats. All had one remnant kidney in which the nephron population was reduced by approximately 80%. In the first two groups, the contralateral kidney was intact; in one of these, micropuncture studies were performed on the intact kidneys and in the other on the remnant kidneys. In the remaining two groups the intact kidneys were removed and the remnant kidneys were studied at one of two time intervals: 1) within 50 hours of removing the intact kidneys; 2) two to three weeks post-nephrectomy. Free flow micropuncture techniques were used to measure single nephron GFR and proximal tubular sodium reabsorption by superficial nephrons. All animals were maintained on a constant daily salt intake by tube feeding. During the studies sodium was infused at a rate adjusted to produce a modest natriuresis. In both acutely and chronically uremic animals fractional sodium excretion was markedly greater than in control animals with the same estimated degree of ECF volume expansion. Single nephron GFR was increased in the uremic animals but absolute sodium reabsorption was not significantly different from the values in the control group. A substantial reduction in fractional sodium reabsorption by proximal tubules was observed. The data suggest that both hyperfiltration and inhibition of proximal tubular sodium reabsorption contributed to the increased rate of sodium excretion per nephron in the uremic rats.