Chen H. Hsu

Cardiac output and renal blood flow in glycerol-induced acute renal failure in the rat.

SUMMARY Cardiac output (CO) and renal blood How (RBF) were simultaneously evaluated by the microsphere method in water-drinking and chronic saline-drinking rats at 3, 12, and 24 hours after induction of acute renal failure by glycerol injection. Three hours after glycerol injection CO and RBF decreased to 36% and 20% of the respective controls in water-drinking rats and to 41% and 24% of the controls in saline-drinking rats. Renal vascular resistance (RVR) increased significantly in both groups at this time. Isoncotic plasma expansion (3% of body weight) restored the RBF and RVR to normal in water-drinking rats 3 hours post-glycerol injection, although CO increased to only 70% of the control. Twelve hours after glycerol injection, CO and RBF returned to normal in saline-drinking rats, whereas they remained lower than controls in water-drinking rats. Twenty-four hours post-glycerol injection, when acute renal failure was evident as indicated by blood urea nitrogen (BUN) values of 116.9 and 63.8 ing/100 ml in water- and saline-drinking rats, respectively, CO and RBF returned to normal, except that the CO of water-drinking rats was slightly higher than control. Thus, we conclude that decreased CO is an important determinant of the early decrease in renal perfusion in glycerol-induced acute renal failure. Furthermore, the observed earlier return of CO and RBF to normal in saline-drinking rats may be partly responsible for reducing the severity of acute renal failure.

Renal cortical blood flow in glycerol-induced acute renal failure in the rat.

Renal hemodynamics and renal function were evaluated in rats at 3, 24. and 48 hours and at 7 days after the induction of acute renal failure (ARF) by glycerol injection. Three hours after induction of ARF, creatinine clearance was 0.04 ml/min/lOOg; renal blood flow (RBF), 1.99 ml/min/IOOg; and filtration fraction, 3.7Z. All were abnormally low. Although the administration of isotonic saline (total dose, 3% of body weight) to rats 3 hours after glycerol injection significantly improvedcreatinine clearance (0.17 ml/min/100 g), RBF (2.54 ml/min/100 g), and filtration fraction (12.9%), these values still were significantly lower than those of controls (creatinine clearance = 0.50 ml. ml/min/100 g, RBF = 4.92 ml/min/100 g, filtration fraction = 20 .0%, all P values <0.001). Serum creatinine concentrations were significantly elevated at 24 hours (3.72 gm/100 ml), 48 hours (4.69 mg/100 ml), and 7 days (0.66 mg/100 ml) after glycerol injection compared to control (0.46 mg/100 ml, all P <0.01). RBF during these phases was not different from normal (4.41 ml/min/100 g). RBF 3 hours after bilateral ureteral obstruction was measured to determine the effects of tubular obstruction on renal hemodynamics. The RBF of rats with ureteral obstruction (4.12 ml/min/IOOg) was not significantly different from controls (4.41 ml/min/100 g), suggesting that tubular obstruction in this model of ARF is probably not the cause of decreased RBF. The depressed glomerular filtration, as reflected by the decreased creatinine clearance that occurs during glycerol-induced ARF, is probably related to altered intrarenal vascular resistance or to changes in glomerular capillary permeability, or both.

Potentiation of gentamicin nephrotoxicity by metabolic acidosis.

Summary Gentamicin nephrotoxicity was examined in normal rats and in rats chronically ingesting 1% NH4C1 solution. Metabolic acidosis significantly exacerbated gentamicin nephrotoxicity as manifested by elevation of SUN and depression of tissue uptake of PAH and TEA by renal cortical slices. In contrast normal rats given the same dose of gentamicin did not develop nephrotoxicity. Pathological examination confirmed that acute tubular necrosis occurred only in the acid-loaded rats injected with gentamicin.

Bicarbonate Hemodialysis: Influence on Plasma Refilling and Hemodynamic Stability

The present study compares the effect of sodium bicarbonate (LoNaHCO3, Na = 134, HCO3 = 33 mEq/l) and sodium acetate (LoNaAc, Na = 134, acetate 33 mEq/1)dialysate on the extravascular fluid mobilization (VFM) and hemodynamic changes in 6 patients during 3 h of hemodialysis with equivalent fluid ultrafiltration of about 600 ml/h. The cumulative decrease in plasma volume after 1, 2 and 3 h of dialysis was significantly less during LoNaHCO3 dialysis than during LoNaAc dialysis, with plasma volume almost completely refilled by VFM during the first 2 h of LoNaHCO3 dialysis. High sodium acetate dialysate (HiNaAc, Na = 144, acetate = 33 mEq/1) with equivalent fluid ultrafiltration also resulted in less net decrease in plasma volume and greater VFM than LoNaAc, although the temporal pattern of refilling was somewhat different from that during LoNaHCO3: rapid and complete refilling during the early portion of LoNaHCO3, slower and more progressive refilling during HiNaAc, with similar cumulative refilling for LoNaHCO3 and HiNaAc by 3 h. Mean arterial pressure (MAP) tended to decrease during LoNaAc dialysis, whereas MAP remained stable during LoNaHCO3 and increased slightly during HiNaAc. This study, therefore, suggests that improved hemodynamic stability utilizing bicarbonate dialysate may be due, in part, to greater plasma refilling and better preservation of plasma volume.

Renal Hemodynamics in HgCl2-Induced Acute Renal Failure

Renal blood flow (RBF), outer cortical blood flow (OC-rbf) and inner cortical blood flow were determined by the microsphere method in water-drinking rats and chronic saline-drinking rats at 3, 12 and 24 h after injection of HgCl2, 4.7 mg/kh body weight. RFB and OC-rbf were decreased in both groups at 3 h post HgCl2 injection. Persistent reduction of OC-rbf was noted in water-drinking rats at 12 and 24 h post HgCl2 even though the total RBF returned to normal by 24 h. These parameters were normal in chronic saline-drinking rats. Despite normal RBF in water-drinking and saline-drinking rats, serum creatinines were still signigicantly elevated 24 h post HgCl2. Therefore, alterations in total renal perfusion do not entirely account for the decreased renal function that occurs under these circumstances.

In vitro uptake of gentamicin by rat renal cortical tissue.

The mechanism of gentamicin uptake in vitro by renal cortical slices of rat kidney was investigated. The cortical-slice-uptake ratio of gentamicin concentration in 1.0 g of tissue water to that of 1.0 ml of incubation medium (SW/M) was 1.44 ± 0.04. The uptake of gentamicin was inhibited by 2 × 10−5 M dinitrophenol (SW/M = 1.03 ± 0.04) and by anoxia (SW/M = 1.01 ± 0.04). The results indicate that aerobic phosphorylation is required to transport gentamicin into the cells. The uptake of p-aminohippurate and tetraethylammonium chloride by renal cortical slices was not affected by gentamicin.

Effect of exogenous angiotensin II on renal hemodynamics in the awake rat. Measurement of afferent arteriolar diameter by the microsphere method.

We measured cardiac output (CO), renal blood flow (RBF), renal plasma flow (RPF), and afferent arteriolar diameter by the microsphere method, and inulin clearance (GFR) simultaneously in awake rats given an infusion of exogenous angiotensin II (100 ng/min per kg). Angiotensin II did not affect the CO, whereas both RBF and RPF decreased significantly in rats infused with angiotensin II (RBF, 2.88 ± 0.11, mean ±SE; RPF, 1.78 ± 0.09, n = 6) when compared to control animals given saline (RBF, 4.58 ± 0.31; RPF, 2.80 ± 0.24 ml/min per 100 g, n = 6, both P < 0.005, respectively). Both mean arterial pressure (MAP) and renal vascular resistance (RVR) were significantly higher in rats infused with antiogensin II than in controls. The decrease in GFR did not parallel the reduction of RPF in rats infused with angiotensin II as reflected by their higher values of mean filtration fraction (41.1 ± 1.6%, n = 6) than that of controls (33.7 ± 2.4%, n = 6, P < 0.05). Despite significant elevations of MAP and RVR in rats infused with angiotensin II, their mean afferent arteriolar diameter (19.6 ± 0.24 /im) was not different from that of controls (20.1 ± 0.39 /im). We conclude that angiotensin II preferentially acts at the site of postglomerular vasculature but not at the afferent arteriole. Circ Res 46: 646-650, 1980

Measurement of Renal Blood Flow in the Rat

A radioactive microsphere technique has been developed for the measurement of renal blood flow and intrarenal blood flow distribution in the dog (1, 2). Various techniques have been proposed (3-5) for the measurement of renal blood flow (RBF) in the rat in addition to the conventional PAH clearance method. This study presents a simple method for the assessment of RBF in rats using radioactive microspheres. Method. Eight male Sprague-Dawley rats weighing 200-240 g were fed with Purina Lab Chow and given tap water ad lib. All animals were lightly anesthetized with ether and cannulated with polyethylene tube No. 10 (i.d. 0.011 in., o.d. 0.024 in.) through the femoral artery for blood collection and through the carotid artery into the left ventricle for injection of microspheres. After awakening from anesthesia, animals were placed in restraining cages and allowed to recover for 45-60 min prior to injection. Radioactive microspheres, 15 μm ± 5 μm diameter, (3m Co., St. Paul, MN) were utilized to measure renal blood flow (RBF) and its intracortical distribution. Two different nuclides were used, 85Sr and 141Ce, for two separate measurements taken 1 hr apart. For each measurement, approximately 0.1 ml of 2 mg/ml concentration of microspheres in 10% dextran was injected through the carotid artery catheter within 5-7 sec. Just prior to injection, the spheres were sonicated for 5-10 min and then vigorously agitated with a vortex mixer for at least 3 min. Immediately upon injection of the spheres into the left ventricle, the femoral catheter was opened and blood was allowed to flow freely into a preweighed tube for exactly 1 min. Approximately 0.2 ml of blood was collected from the femoral artery in each minute. The adequacy of 1-min collection periods, vis à vis complete removal of microspheres from the circulation, was tested in a separate group of five animals.

Familial Azotemia: Impaired Urea Excretion despite Normal Renal Function

We performed detailed studies of renal function in two of five related patients with normal serum creatinine levels to determine the mechanism of their chronic azotemia. Inulin and para-amino-hippurate clearances, maximum tubular transport of para-aminohippurate, and renal acidification were within normal limits. In addition, renal concentrating and diluting abilities of these patients were similar to those of four normal controls. Urea clearances of both patients during maximum water diuresis (27.6 and 40.8 ml per minute per 1.73 m2) and antidiuresis (5.3 and 4.0), however, were much lower than mean (+/- S.E.M.) values in the normal controls (70.4 +/- 3.7 and 30.0 +/- 3.42 ml per minute per 1.73 m2, respectively). Thus decreased urea excretion despite otherwise normal renal function was responsible for the chronic azotemia of these patients. The genetic defect in renal urea clearance appeared to be inherited as an autosomal dominant trait.

Intrarenal Hemodynamics in Acute Myohemoglobinuric Renal Failure

Renal blood flow (RBF) and its distribution were measured in acute renal failure induced by glycerol injection to water-drinking rats and to rats chronically loaded with NaCl solution. Mean RBF and intracortical blood flow distribution of both water-drinking and saline-loaded rats at 24 h after glycerol injection were not different from those of control rats. Although chronic saline loading blunted the impairment of renal function caused by glycerol as evidenced by serum creatinine values, no differences in renal hemodynamics were noted. This suggests that changes in glomerular arteriolar resistance or glomerular permeability might be of greater importance in the reduction of glomerular filtration rate than are alterations of blood flow.