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Biomedical subjects

E A Alexander

Publications and source records attributed to E A Alexander.

At least 73 records · Page 4Linked to original sources
PubMed1978

Renal sodium retention during volume expansion in experimental nephrotic syndrome.

We have studied sodium retention during volume expansion in rats with autologous immune complex nephropathy (AICN), a model of nephrotic syndrome (NS) in which GFR after volume expansion was not different from that in adjuvant-injected controls (C). AICN rats developed heavy proteinuria (298 +/- 27 vs. less than 10 mg/day), hypoalbuminemia (2.14 +/- 0.15 vs. 3.08 +/- 0.12 g/100 ml) and hypercholesterolemia (181 +/- 22 vs. 58 +/- 4 mg/100 ml). After saline, there were no significant differences in blood pressure (119 +/- 2 vs. 114 +/- 2 mm Hg), renal plasma flow (4.9 +/- 0.41 vs. 4.1 +/- 0.28 ml/min), inulin clearance (1.37 +/- 0.06 vs. 1.55 +/- 0.10 ml/min), or SNGFR (47 +/- 2 vs. 53 +/- 4 nl/min). Sodium excretion, however, was significantly lower in NS rats (4.7 +/- 1.1 vs. 9.2 +/- 1.2 muEq/min). Proximal sodium reabsorption was decreased in NS rats (35 +/- 2 vs. 41 +/- 2%, 2.5 +/- 0.2 vs. 3.3 +/- 0.2 nEq/min). Sodium delivery into the loop, however, was equal in NS and C, since the slightly lower filtered load in NS rats offset the depression in proximal reabsorption. Sodium reabsorption by the loop and by the distal convoluted tubules were equal in NS and C. Thus, sodium delivered into the cortical collecting ducts was the same in both groups (0.33 +/- 0.17 vs. 0.34 +/- 0.07 nEq/min; 4.5 +/- 0.6% of filtered sodium vs. 4.4 +/- 0.3%). The percent of filtered sodium excreted in the urine, however, was significantly lower in the NS rats, 2.18 +/- 0.48% vs. 4.0 +/- 0.58%. We conclude that antinatriuresis in this model of NS is determined beyond the superficial late distal convoluted tubule. The inability to excrete the sodium load during volume expansion is due to either enhanced reabsorption by the collecting duct or to abnormal function in deep nephrons.

Animals↗
PubMed1978

Tubular sites of potassium regulation in the normal and uninephrectomized rat.

Tubular handling of potassium was studied in the Charles River CD (cesarean derived) rat by clearance, micropuncture, and anatomic techniques. The following groups were evaluated: group I, hydropenia; group II, KCl-mannitol infusion; group III, 10% body wt saline loading; group IV, uninephrectomy, hydropenia; and group V, uninephrectomy, saline loading. Comparison of micropuncture samples from early and late distal collection sites (LDCS) and urine collections revealed no net K transport along the distal convoluted tubule in groups I and III-V but net addition of K in all groups beyond the LDCS. Absolute K secretion beyond the LDCS appeared to be flow dependent in groups I-III. The LDCS was noted by light and electron microscopy always to be lined with collecting tubule epithelium. We conclude that no net change in potassium transport occurs along the superficial distal convoluted tubule during hydropenia or saline loading in normal or uninephrectomized Charles River CD rats, but secretion is demonstrable during KCl infusion. Net addition of potassium beyond the LDCS was noted in all groups and this addition was enhanced by uninephrectomy.

Animals↗
PubMed1977

Natriuresis after adrenal enucleation: effect of spironolactone and dexamethasone.

After adrenal enucleation, rats have an impaired ability to excrete a salt load because of enhanced collecting duct reabsorption. This antinatriuretic effect, thought to be secondary to a mineralocorticoid-like substance secreted by the enucleate gland, can be reversed by treatment with spironolactone or dexamethasone. To define the renal mechanisms involved in this drug-induced natriuresis we have utilized clearance and micropuncture techniques in enucleate saline-expanded rats that were treated with either spironolactone (S) or dexamethasone (D), or were untreated (U). Sodium excretion was clearly increased after S, 13.9, and D, 19.3 mueq/min vs. u, 5.9 mueq/min. The mechanisms of this natriuresis, however, were dissimilar. Spironolactone-treated rats were not different from untreated rats except with regard to function beyond the superficial late distal tubule, where U rats reabsorbed over 50% of the delivered sodium. In the S group 38% of the excreted sodium was added along this tubular locus, 5.2% of the filtered sodium reaching the late distal tubule and 7.3% appearing in the urine. These data demonstrate that the natriuresis after S is secondary to the net addition of sodium beyond the superficial late distal tubule. Spironolactone may work by inhibiting a mineralocorticoid-like product of the enucleate gland and, thereby, eliminate the sodium-retaining effect of this product. The natriuresis after D, however, can be explained solely on the basis of a markedly increased filtered load of sodium traversing the nephron.

Adrenalectomy↗
PubMed1977

Evidence that decreased cardiac output is not the stimulus to sodium retention during acute constriction of the vena cava.

It has been proposed that the antinatriuresis during constriction of the TVC is due to a decrease in CO. We have compared the effect on sodium excretion of comparable reductions in CO by three separate methods: TVC constriction, PA occlusion, and LV infarction. Dogs were studied during 10% of body weight saline loading and again after TVC constriction, PA occlusion, or LV infarction. CO fell 26 to 31% in all groups; sodium excretion was not significantly altered after PA occlusion (474 to 533 micronEq/min.) or LV infarction (587 to 609 micronEq/min.) but fell significantly after TVC constriction (504 to 271 micronEq/min.). Renal and systemic hemodynamoderate reduction of CO per se does not cause sodium retention. PA and TVC dogs had comparable increments in vena caval pressure but opposite changes in RVEDP; 4 to 0.9 mm. Hg (TVC) and 0.5 to 9.1 mm. Hg (PA).

Animals↗
PubMed1977

Renal failure in Burkitt's lymphoma.

A case of Burkitt's lymphoma with renal failure due to massive infiltration of the kidney is reported. There was a striking initial response to chemotherapy with a parallel improvement in renal function and decrease in renal size. The rare occurrence of renal failure due to lymphomatous infiltration of the kidney parenchyma in the absence of urinary tract obstruction is reviewed.

Acute Kidney Injury↗
PubMed1976

Effect of adrenal enucleation on sodium excretion in the rat.

After the adrenal glands are removed without their capsules, so-called adrenal enucleation, rats initially retain sodium, and, after adrenal regeneration, escape from salt retention. To define the renal mechanisms involved in this alteration in salt handling, we have utilized clearance and micropuncture techniques in three groups of saline-expanded rats that were sham-operated (S), enucleated (AE), or escaped after adrenal regeneration (E.) Sodium excretion was clearly blunted after AE, 5.5 mueq/min vs. 20.5 for S and 18.7 for E. Although glomerular filtration rate (GFR) and filtered load of sodium were lower in AE rats, the delivered load of sodium beyond the late distal tubule was not different among the groups: 0.30 neq/min for AE, 0.42 for S, and 0.40 for E. This was a consequence of strikingly greater sodium reabsorption in the loop of Henle and distal tubule in both the S and E rats. In the collecting duct over 50% of the delivered sodium was reabsorbed by the AE rats while over 30% of the excreted sodium was added in this tubular segment in the other groups. These data demonstrate that the impaired natriuresis after adrenal enucleation appears to be due to striking differences in collecting duct function. Since adrenal regeneration in the escape animals reverses this sodium retention, the effect is probably related to some alteration in adrenal hormone production. Sodium excretion in markedly expanded normal rats also appears to be determined by the net addition of sodium in the collecting duct.

Adrenal Glands↗
PubMed1975

The effect of ischemia on renal blood flow in the dog.

Renal blood flow (RBF) and the distribution of cortical blood flow (microspheres) were measured in the dog after 90 min of total unilateral renal ischemia. RBF was 21% greater than control 2 min after release of the renal artery occlusion, and returned toward control 60 min later. At 2 min after release there was a small but significant increment in deep cortical blood flow which reverted to control by 60 min. When renal artery occlusion was maintained for 180 min, return of blood flow was blunted at 2 min after release of the occlusion, but was not significantly different from control within 10 min after release. Clearance rates of inulin and para-aminohippurate (Cin and Cpah) were 81 and 82% below control after release of occlusion. These data demonstrate that in the dog there is prompt and complete return of blood flow to or above control levels after complete renal artery occlusion. There was no evidence for the "no-reflow" phenomenon.

Aminohippuric Acids↗
PubMed1975

Effect of hemodilution on the distribution of renal blood flow.

We evaluated the effects of hemodilution, expansion of intravascular volume, and expansion of interstitial volume on the distribution of cortical renal blood flow, utilizing the microsphere technique. Hemodilution without volume expansion (saline exchange) produced an increase in fractional blood flow in zone 1 (outermost zone) of the cortex from 34 plus or minus 1% to 43 plus or minus 2% and a decrease in fractional blood flow in zone 4 (innermost zone) from 16 plus or minus 2% to 13 plus or minus 2%. Hemodilution without volume expansion or a decrease in plasma protein concentration (isoncotic exchange) produced a similar redistribution in blood flow in zone 1 from 34 plus or minus 2% to 41 plus or minus 2% and in zone 4 from 14 plus or minus 2% to 10 plus or minus 1%. Hemodilution with intravascular volume expansion (hyperoncotic albumin infusion) also produced a superficial shift; blood flow in zone 1 increased from 27 plus or minus 1% to 30 plus or minus 1% and that in zone 4 decreased from 19 plus or minus 2% to 15 plus or minus 1%. Previous studies have demonstrated a redistribution to the juxtamedullary area after saline expansion. Our data demonstrate that hemodilution causes flow to redistribute to the superficial rather than the deep cortex. This superficial shift appears to be secondary to decrease hematocrit rather than to dilution of plasma proteins or expansions of intravascular volume. The deep shift in cortical blood flow which occurs during saline loading is presumably a consequence of expansion of interstitial volume.

Animals↗
PubMed1975

Nephrotoxicity associated with cephalothin administration.

Variable degrees of acute renal failure developed in three patients receiving therapy with cephalothin sodium. The course and findings were consistent with acute tubular necrosis of the oliguric and nonoliguric types. One patient had protracted oliguria, a second experienced transient oliguria, and one had normal urine output. All had urinary sediment changes consistent with tubular necrosis, and the two oliguric patients had elevated urine sodium concentrations. No other causes for renal failure could be detected, and all recovered after discontinuation of cephalothin therapy, although peritoneal dialysis was required in one patient. These observations indicate that cephalothin is capable of inducing renal damage in man.

Acute Kidney Injury↗
PubMed1974

Superficial and juxtamedullary nephron function during saline loading in the dog.

A modification of the microdissection technique of Hanssen was utilized in dogs to measure superficial (SNGFR) and juxtamedullary nephron filtration rate (JMGFR) in control and saline-expanded dogs. During control studies SNGFR was 60+/-4 and JMGFR was 72+/-5 nl/min. During saline loading SNGFR was 74+/-8 and JMGFR was 65+/-6 nl/min. The ratio SNGFR: JMGFR significantly increased from 0.84+/-0.03 to 1.15+/-0.08. Glomerular perfusion rate (GPR) was measured with the microsphere method during control and saline loading. Superficial GPR did not change significantly but juxtamedullary GPR increased from 225+/-42 to 323+/-39 nl/min. Calculated superficial nephron filtration fraction was unchanged after saline expansion but juxtamedullary filtration fraction decreased from 0.34+/-0.07 to 0.24+/-0.07. The data demonstrate a tendency for filtration to shift toward the superficial part and plasma flow toward the deep part of the kidney cortex. GFR in juxtamedullary nephrons appears to be less plasma flow-dependent than in superficial nephrons. The fall in filtration fraction in the deep cortex may affect sodium excretion by juxtamedullary nephrons.

Animals↗
PubMed1972

Restoration and maintenance of glomerular filtration by mannitol during hypoperfusion of the kidney.

Glomerular filtration (GF) during progressive reduction of renal perfusion pressure by aortic clamping was studied in hydropenic rats and in rats infused with isotonic saline, hypertonic saline, or mannitol. As judged by visual observation of Lissamine green movements in superficial nephrons. GF was absent in hydropenic or saline-loaded rats at 40 mm Hg aortic pressure, but continued in some nephrons of all rats infused with mannitol and of some rats infused with hypertonic saline. Urine flow persisted only in rats infused with mannitol. By use of the qualitative Hanssen technique, it was found that all glomeruli in superficial and deep portions of the cortex were perfused at 40 mm Hg in all groups of rats. By the same method. GF continued in 1% of nephrons in hydropenic rats, 12% of nephrons in isotonic saline-loaded rats, and 78% of nephrons in rats infused with mannitol. By means of a quantitative Hanssen technique, GF was 5.8 nl/min per nephron in mannitol-infused rats and not measurable (< 0.5 nl) in hydropenic rats. Superficial and deep nephrons were similar in both qualitative and quantitative studies. Although urine flow did not persist in rats infused with hypertonic saline, GF was detected in four of seven studies by the Hanssen method (mean, 9.1 nl/min per nephron). In additional experiments, mannitol infused after perfusion pressure had already been lowered to 40 mm Hg in hydropenic rats reestablished urine flow and GF (mean, 9.8 nl/min). Furosemide, isotonic and hypertonic saline did not restart urine flow; however, GF (Lissamine green) was restarted by hypertonic saline. We conclude that mannitol can maintain or reestablish by an extratubular mechanism GF which otherwise would not occur during renal hypoperfusion. Hypertonic saline has a similar effect on GF in some cases, but urine flow is not maintained, implying complete reabsorption of filtrate.

Animals↗
PubMed1972

Tubular reabsorption of sodium during acute and chronic volume expansion in man.

Renal hemodynamics and tubular fractional sodium reabsorption (FSR) were evaluated by clearance techniques during acute and chronic extracellular volume expansion in man. (1 - V/GFR) x 100 was used as an index of proximal and (C(H2O)/V) x 100 as an estimate of distal fractional reabsorption. After acute loading with isotonic saline 37 ml/kg body wt, proximal FSR decreased by 4.8% and distal FSR decreased by 4.4%. After comparable chronic expansion by mineralocorticoids ("escape"), proximal FSR also decreased by 3.9%, but distal reabsorption was not altered.In separate studies, subjects were progressively infused with saline to 57 (E(1)) and to 80 (E(2)) ml/kg body wt, and appeared to divide into "excreters" (maximum U(Na)V > 1000 muEq/min) and "nonexcreters" (maximum U(Na)V < 550 muEq/min). In the excreters, GFR rose, proximal FSR decreased by 7.1% after E(1) and only 0.9% further after E(2). Distal FSR fell by 14.8% after E(1) and by an additional 4.9% after E(2). In the nonexcreters, GFR was stable and proximal FSR did not fall significantly after E(1) or E(2). Distal FSR decreased 4.5% after E(1) and 1.3% further after E(2). It is concluded that both acute and chronic extracellular expansion decrease proximal FSR in man, but only acute loading depresses distal FSR. Ability of some men to excrete sodium rapidly after acute infusion is related to larger increases in GFR and greater decreases in both proximal and distal FSR than occur in men in whom natriuresis is more limited.

Adult↗