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Biomedical subjects

A Besarab

Publications and source records attributed to A Besarab.

30 records · Page 2Linked to original sources

Effect of catecholamines on tubular function in the isolated perfused rat kidney.

Addition of norepinephrine or epinephrine to the isolated rat kidney perfused at constant pressure resulted in an increase in sodium reabsorption and the excretion of a dilute urine with an increase in free water clearance. Vasopressin reversed the fall in urinary osmolarity but not the diminution in sodium excretion. The urinary changes produced by catecholamines were blocked by propranolol but not by phenoxybenzamine, suggesting that they were mediated, at least in part, by beta receptors. Similar though less pronounced changes in sodium excretion and urinary osmolarity were produced by isoproterenol and phenylephrine, while the combination of these drugs induced marked dilution of the urine. The results suggest that circulating catecholamines or adrenergic nerves innervating the kidney directly influence renal tubular function and might, therefore, participate in the regulation of sodium and water excretion by the kidneys.

Animals

Reversible renal failure following bilateral renal artery occlusive disease. Clinical features, pathology, and the role of surgical revascularization.

Three patients with severe hypertension and rapidly progressive oliguric renal failure who required dialysis were found by aortography to have bilateral renal artery occlusion or stenosis. Each had peripheral arteriosclerosis or an abdominal bruit. Following renal artery reconstructive surgery, all three patients recovered nearly normal renal function in 3 to 12 weeks, though mild hypertension persisted in two patients. The common findings of a normal-sized kidney with collateral blood flow and nearly normal histological features were predictive of recovery of renal function. Prolonged postoperative oliguria in two patients may have been due to increased preglomerular vascular resistance mediated by the renin-angiotensin system.

Acute Kidney Injury

Multiple pumps for sodium reabsorption by the perfused kidney.

Several distinct transport mechanisms responsible for sodium reabsorption by the rat kidney can be identified by studying the function of isolated perfused kidneys. Approximately one-half of the fractional sodium reabsorption by the isolated perfused rat kidney appears to depend on Na-K-adenosine triphosphatase (AT-Pase) and is inhibited by ouabain. About 10 to 20% is associated with the reabsorption of bicarbonate and is blocked by acetazolamide. This fraction of transported sodium is unaffected by ouabain and therefore does not involve Na-K-ATPase. Neither furosemide nor ethacrynic acid produce further inhibition of sodium reabsorption in a kidney already exposed to ouabain and acetazolamide. Most of the residual transport of sodium is inhibited by cooling the perfused kidney, suggesting that it is powered by metabolic rather than physical sources of energy.

Acetazolamide

Bicarbonate and sodium reabsorption by the isolated perfused kidney.

The role of bicarbonate reabsorption and of transtubular chloride gradients in the bulk reabsorption of sodium and water by renal tubules can be tested in the isolated perfused kidney by perfusing with a medium from which bicarbonate has been omitted. Perfusion of the isolated rat kidney with an artificial medium in which bicarbonate is replaced by chloride results in a fall in fractional reabsorption of sodium from 97 to 84%. Stepwise restoration of bicarbonate concentration in the perfusion medium to 25 meq/liter is associated with a parallel recovery of sodium reabsorption to control levels. Inhibition of bicarbonate reabsorption with acetazolamide produces a slightly smaller reduction in sodium reabsorption (97-89%), an effect not seen in the absence of bicarbonate. Acetazolamide greatly increases phosphate excretion and free water clearance in a way consistent with suppression of proximal tubular reabsorption. By contrast, simple omission of bicarbonate from the perfusing medium does not alter phosphaturia or free water clearance. Reabsorption of bicarbonate appears to account for a fraction of sodium reabsorption roughly equivalent to the proportion of sodium associated stoichiometrically with bicarbonate in the glomerule filtrate. The data do not support the hypothesis that the development of a transtubular chloride gradient is critically important for the reabsorption of a large fraction of the glomerular filtrate.

Acetazolamide

Potassium transport by the isolated perfused kidney.

Rat kidneys perfused outside of the body with an artificial medium are able to increase their fractional excretion of potassium in response to a rising concentration of potassium in the medium but never show net secretion of potassium. By contrast, isolated perfused kidneys from chronically potassium-loaded rats regularly secrete potassium in excess of the amount filtered. Ouabain completely blocks the secretion of potassium by these isolated kidneys, suggesting that Na-K-ATPase mediates potassium secretion by potassium-adapted rats. Neither sodium deprivation, pretreatment with deoxycorticosterone, nor pretreatment with methylprednisolone prepared the kidney to secrete potassium, despite stimulation of Na-K-ATPase activity in cortex or outer medulla. Potassium loading was the only maneuver tested that increased the activity of Na-Katpase in the inner medulla (white papilla) and also produced potassium secretion by the isolated kidney. Surgical ablation of the papilla abolished the net secretion of potassium normally seen in perfused kidneys of potassium-adapted rats, thus underlining the importance of the papilla in the process of potassium adaptation.

Adaptation, Physiological

Sensitivity of in vivo X-ray fluorescence determination of skeletal lead stores.

Eighteen patients with known past occupational lead exposure underwent parenteral diagnostic chelation with ethylenediaminetetraacetic acid and x-ray fluorescent determination of in vivo skeletal lead stores at the distal styloid process of the ulna and at the temporal base bone using a cobalt 57 source and measuring lead Ka x-rays. X-ray fluorescent lead measurements in both locations correlated with results of diagnostic chelation. Using a post-chelation urinary excretion of greater than 600 micrograms lead/24 h as the definition of "high-" lead stores, sensitivity of x-ray fluorescence at the wrist and temple was 56% and 39%, respectively.

Bone and Bones

Venous access pressures and the detection of intra-access stenosis.

Venous pressure measured by the dialyzer is an unreliable measure of intra-access venous pressure. During dialysis and zero extracorporeal blood flow, intra-access venous limb pressure (VPd) was measured directly 401 times in 133 subjects using a high flow "in-line" three-way stopcock adjacent to the venous return needle. Subjects with systolic VPd/systolic blood pressure (BP) > or = 0.4, inadequate blood flow, or edema in the access extremity were referred for angiography. Percent diameter lumen reduction by a stenosis (%D) > 50% was considered hemodynamically significant. The authors did 138 angiograms. It was found that VPd/BP increased with %D in both ePTFE bridge grafts and native fistulae. Measurements of venous limb VP/BP taken at the time of dialysis and at the time of angiography did not differ (n = 55). On 80 occasions, accesses had significant stenoses. The overall sensitivity of VPd/BP in ePTFE bridge grafts was 91% and specificity 91%. False negative results occurred in seven of 24 native and eight of 114 ePTFE graft studies; 14 of 15 patients had arm swelling caused by central stenosis. Recirculation > 15% was more sensitive (71%) in detecting stenosis in native accesses than was intra-access pressure. It was concluded that VPd/BP > 0.4 is a useful, sensitive, and specific criteria for detecting synthetic bridge graft accesses at risk for thrombosis.

Angiography

Effects of dialysis factors and route of administration on response of hemodialysis patients to recombinant human erythropoietin.

Data on the use of recombinant human erythropoietin (rHuEPO) were obtained from 25 hemodialysis centers to determine whether route of administration (intravenous [i.v.] vs. subcutaneous [s.c.]) or various dialysis factors influenced the response to rHuEPO; 844 of 958 patients had sufficient data for evaluation. Hematocrit (HCT) increased from 23.8 to 29.1% after a mean rHuEPO treatment period of 202 days; 48.4% of all patients did not reach a HCT greater than or equal to 29%. The s.c. route increased HCT more than the i.v. route. Multivariate analysis of the response (i.e., increase in HCT from baseline) showed a positive correlation with more rapid dialysis but a negative correlation with reuse, baseline HCT, transfusion dependence, and frequency of administration. The effects of dialysis and reuse were not present when the response was normalized by weekly dose. It was concluded that one half of all patients treated did not attain the recommended target HCT, perhaps due to economic constraints or resetting of goals. The s.c. route may be preferable to optimize response.

Drug Administration Schedule

Determinants of measured dialysis venous pressure and its relationship to true intra-access venous pressure.

Venous pressure measured at the venous bubble trap (VPdm) is a complex function of true intra-access pressure (VP0), hematocrit, needle gauge, and blood flow. In a patient free circuit, needle gauge, hematocrit, and blood flow influenced the pressure drop through the venous return needle. Measured intra-access pressure (VPm) and VPdm also were determined 149 times in 83 subjects. The increase in VPdm above VP0 under conditions of flow through 16 gauge needles was affected by blood flow rate, hematocrit, and VP0 with coefficients similar to those found in vitro. Calculation of VP0 from VPdm produced an absolute difference greater than 20 mmHg in 35-40% of cases. Mean VP0 was significantly lower in subjects with native compared with expanded polytetrafluorethylene accesses. It was concluded that VP0 is influenced by access type and can be estimated but that direct measurement is preferred. Direct measurement of VP0 may be a sensitive test to screen for venous outlet stenosis because it should vary with access flow and outlet geometry.

Arteriovenous Shunt, Surgical

Response of continuous peritoneal dialysis patients to subcutaneous recombinant human erythropoietin differs from that of hemodialysis patients.

The hematologic response of 65 continuous ambulatory peritoneal dialysis (CAPD) patients to subcutaneous recombinant human erythropoietin (rHuEPO) was compared with that of 369 hemodialysis patients (HD). Pretherapy transfusions were more common in HD than CAPD. The response was measured as the change in hematocrit after 70 or more days of therapy (or as the hematocrit change normalized by a weekly dose) in CAPD patients. The weekly rHuEPO dose did not differ, but the dosing frequency was less in CAPD than in HD patients. Hematologic response parameters were greater in CAPD. Multivariate analysis showed that the response in both groups varied inversely with the frequency of dosing and with pretherapy baseline hematocrit. In HD subjects, the response also varied inversely with previous transfusion history. The authors concluded that CAPD patients responded better to rHuEPO than HD patients. This may be a result, in part, of lower ongoing blood losses. Patients with more severe anemias responded less well, whereas more sensitive patients were dosed less frequently.

Dose-Response Relationship, Drug

Recombinant human erythropoietin does not increase clotting in vascular accesses.

The incidence of vascular access clotting was evaluated over 5.25 years. The first 32 months served as a control period. During the second period of 31 months, recombinant human erythropoietin (epoetin) was used for an average duration of 13 months (range, 2-32 months) in 79 patients. The overall incidence of vascular access clotting decreased from a monthly rate of 0.06 to 0.03 events per patient-month over the 5 year period. Distribution of the number of events per patient did not differ between the two periods, with 55% to 60% of patients having no clotting episode. Patients with recurrent clotting (two or more events) accounted for 68% of episodes. During the second period, there were no differences in the incidence of vascular access clotting in epoetin treated patients vs untreated patients (0.38 events per patient-year vs. 0.46 events per patient-year, both slightly lower than in period 1 [0.52 events per patient-year]). It is concluded that epoetin does not increase vascular access clotting.

Anemia