intosh II (Apple Computer Inc., Cupertino, CA). The two- tailed Student's t test for unpaired samples was used. Cor- relation between metabolic variables was ...
Rapid Increase in Plasma Levels of Atral Natriuretic Peptide After Common Bile Duct Ligation in the Rabbit
JUAN VALVERDE, M.D.,* FRANCISCO MARTINEZ-RODENAS, M.D.,* JOSE A. PEREIRA, M.D.,* XAVIER CARULLA, M.D.,* WLADIMIRO JIMENEZ, M.D.,t JOSE M. GUBERN, M.D.,* and ANTONIO SITGES-SERRA, M.D.*
Previous studies have shown that common bile duct ligation in the rabbit is followed by a reduction of the extracellular water compartment. To further elucidate the mechanisms leading to volume depletion in this model, water and sodium balances and changes in plasma concentrations of atrial natriuretic peptide (ANP), vasopressin (ADH), plasma renin activity (PRA) and aldosterone (Ald) were investigated during the first 4 days after common bile duct ligation (group OJ,) or sham operation (group SO). Water and chow intakes were lower in group OJ (148 ± 30 versus 226 ± 40 mL/4 days; p = 0.004 and 12 ± 9 versus 171 ± 40 g/4 days; p = 0.0001). There were no differences in urine output. Sodium urinary losses were marginally higher in group OJ (12.4 ± 7 versus 6.7 ± 5 mEq/4 days; p = 0.06). Water balance was lower in group OJ (-50 ± 56 versus 101 ± 71 mL/ 4 days; p = 0.0001). At 24 hours, plasma ANP (41 ± 7 versus 10.7 ± 1 fmol/mL, p = 0.0001), ADH (21.8 ± 7 versus 12.3 ± 6 pg/mL, p = 0.008) and Ald (14.5 ± 5 versus 3.7 ± 3 ng/dL, p = 0.001) were higher in group OJ. These alterations persisted 72 hours after bile duct ligation, when a concomitant increase in PRA (10.7 ± 5 versus 3 ± 1.6 ng/dL, p = 0.006) was also observed. A group of pair-fed pair-watered sham-operated controls (group S02, n = 13) showed a metabolic profile similar to group OJ but a low ANP concentration. Multiple venous sampling in five rabbits 24 hours after bile duct ligation showed the highest plasma levels of ANP in the aorta and infrarenal vena cava. These results suggest that common bile duct ligation in the rabbit is followed by marked hypodipsia and hypophagia, possibly mediated by ANP, leading to isotonic volume depletion and secondary activation of the water and sodium retaining hormones.
EVERAL HYPOTHESES HAVE been put forward to explain the increased frequency and severity of acute renal failure observed in patients with obstructive jaundice, namely, nephrotoxicity of bile components, endotoxinemia, and hemodynamic alterations. Supported by grants 88/1885 and 88/1886 of the "Fondo de Investigaciones Sanitarias de la Seguridad Social." Address reprint requests to Antonio Sitges-Serra, M.D., Departament de Cirurgia, Hospital Universitari del Mar, P. Maritim, 25-29, 08003 Barcelona, Spain. Accepted for publication July 18, 1991.
From the Department of Surgery and Surgical Research Unit,* Hospital Universitari del Mar, Autonomous University of Barcelona and Laboratory of Hormonal Biochemistry, t Hospital ClInic, University of Barcelona, Barcelona, Spain
Preoperative prophylaxis with mannitol" 2 or oral bile salts3 have been advocated to reduce the incidence and severity of this complication. These have not proved to be effective when submitted to prospective controlled trials, however.4'5 The need for a reappraisal of the pathogenesis of renal dysfunction associated with obstructive jaundice has stimulated research in areas such as water and sodium metabolism, heart performance, or endocrine changes. Studies of body water compartments with tracer isotopes in an experimental model of obstructive jaundice have shown that 6 and 12 days after common bile duct ligation there was a 20% and 35% loss, respectively, of extracellular water.6 Plasma volume reduction also was observed in advanced stages. To elucidate the pathophysiology of volume depletion after common bile duct ligation, the water intake and plasma concentrations of atrial natriuretic peptide (ANP) were measured in a subsequent study. A low water intake and high concentrations of ANP were found 4 and 10 days after bile duct ligation.7 Thus, the current investigation was planned to measure water and sodium intakes, water balance, natriuresis, and plasma concentrations of ANP, vasopressin (ADH), aldosterone, and plasma renin activity (PRA) during the first 4 days after common bile duct ligation in the rabbit.
Animals and Methods Animals and Surgical Technique Male New Zealand white rabbits weighing 2500 to 3000 g were used throughout the experiment. Animals were housed in metabolic cages for 7 days before the study to allow for adaptation at a constant room temperature of
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21 'C. Water and chow (Panlab, Barcelona, Spain) were offered ad libitum until the end of the study. A right jugular silicone catheter tunnelized to the interscapular region was inserted in all animals 4 days before laparotomy. At day 0, a median laparotomy was carried out under general anesthesia (ketamine 100 mg/kg and thalamonal 0.5 mL/ kg, intramuscularly). Prophylactic antibiotics were administered at the beginning of the procedure (Cefonicid 125 mg intramuscularly, Smith Kline and French, Madrid, Spain). A double 000 silk ligature or simple dissection of the common bile duct were carried out in the experimental jaundiced group (group OJ, n = 20) and in the control sham-operated group (group SO, n = 17), respectively. Because jaundiced animals exhibited a striking reduction of water and sodium intakes, a third group was added to investigate the metabolic and endocrine changes in pair-fed, pair-watered sham-operated rabbits (S02, n = 13). These animals were offered the same amount (daily mean) of water and chow as that drunk and eaten by the group OJ. Water and chow intakes and diuresis were recorded during the first 4 days after laparotomy. Water balance was calculated by subtracting urine output from water intake without taking into account insensible losses (fecal, respiratory, and integumental). Following manufacturer's instructions, sodium content in chow was estimated at 3.1 mg sodium per gram chow. Plasma sodium, glucose, bilirubin, urea and creatinine, and urinary sodium and creatinine were measured daily in an SMA autoanalyzer (Technicon Instruments Corporation, Tarrytown, New York). Creatinine clearance and free water clearance were derived using standard formulae.
Hormonal Determinations Immediately before anesthesia and laparotomy, blood sampled through the jugular catheter for hormonal determinations (reference basal values). Two additional hormonal determinations were carried out 24 and 72 hours after surgery in six rabbits with bile duct ligation and six sham-operated controls. To investigate the most probable source of increased ANP concentrations, a multiple venous sampling for ANP was carried out by direct vessel puncture, 24 hours after common bile duct ligation, in five additional rabbits. Animals were anesthesized, relaparotomized, and blood samples taken immediately. The venous territories sampled were: (1) right auricle, (2) abdominal aorta, (3) infrarenal vena cava, (4) suprarenal vena cava, and (5) suprahepatic veins-inferior vena cava junction. Atrial natriuretic peptide was determined by radioimmunoassay after extraction with C- 18 Sep-Pack Cartridges (Waters Associates, Milford, MA) as previously described.7'8 Plasma renin activity was measured by radioimmunoassay (Clinical Assay, Baxter, Cambridge, MA) and aldosterone by Coat-A-count (Aldosterone Diwas
555
agnostic and Products Corporation, Los Angeles, CA). Vasopressin was extracted from plasma with cold 98% ethanol and determined by radioimmunoassay (Bulholm Laboratories AG, Basel, Switzerland). The maximum variation coefficient of this assays corresponded to that of ADH with a 10% intra-assay and 14% interassay.
Statistical Analysis Results were analyzed with the Statview II statistical package (Abacus Concepts Inc., Berkeley, CA) in a Macintosh II (Apple Computer Inc., Cupertino, CA). The twotailed Student's t test for unpaired samples was used. Correlation between metabolic variables was investigated with the Pearson's r correlation coefficient. Statistical significance was accepted for p < 0.05. All data are expressed as mean ± 1 standard deviation.
Results Water and Sodium Metabolism Before laparotomy, both groups of rabbits were homogeneous with respect to body weight and water and sodium intakes (Table 1). Metabolic derangements were already apparent at 24 hours after laparotomy (Table 2), group OJ showing a reduced water intake, lower water balance, and higher weight loss. These findings were more marked at 72 hours after laparotomy (Table 3). During the whole period, water and chow intakes were consistently lower in group OJ; urine output was similar in both groups. This is reflected in the cumulative balances carried out at day 4 after laparotomy (Table 4), which showed markedly negative water, sodium, and weight balances in group OJ. There was a close correlation between 4 days' cumulative water balance and weight loss (Fig. 1) for both experimental groups.
Endocrine Changes Before laparotomy, both groups of rabbits were homogeneous in respect to plasma concentrations of ANP, aldosterone, ADH, and PRA (Table 1). Twenty-four hours TABLE 1. Homogeneity Between Groups Before Laparotomy and Common Bile Duct Ligation (Group OJ) or Sham Operation (Group SO)
Weight (g) Water intake (mL/day) Chow intake (g/day) Diuresis (mL/day) ANP (fmol/mL) Aldosterone (ng/dL) ADH (pg/mL) PRA (ng/dL)
Group OJ (n = 17)
Group SO (n = 20)
p
2540 ± 20 102 ± 12 75 ± 6 71 ± 18 12 ± 3.5 2.7 ± 1.6 13 ± 5.4 1.5 ±0.8
2574 ± 22 111 ± 13 71 ± 11 71 ± 42 10.3 ± 4.2 2.5 ± 1.1 9.9 ± 6 1.3 ± 0.4
NS NS NS NS NS NS NS NS
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Ann. Surg. * November 1992
VALVERDE AND OTHERS
TABLE 4. Cumulative Balances 4 Days After Common Bile Duct Ligation (Group OJ) or Sham Operation (Group SO)
TABLE 2. Water and Sodium Metabolism Parameters 24 Hours After Common Bile Duct Ligation (Group OJ) or Sham Operation (Group SO)
Group OJ (n=17)
Group SO (n=20)
9 ± 15 66 ± 30 Water intake (mL) 63 ± 20 58 ± 30 Diuresis (mL) -54 ± 30 3 ± 37 Water balance (mL)* -3.8 ± 2 -5.1 ± 1 Weight loss (%) 4.8 ± 4.2 1.7 ± 1.8 Urinary sodium (mEq) Free water clearance (mL/min) -0.08 ± .04 -0.08 ± .05 2.9 ± 1.3 0.1 ± 0.09 Total bilirubin level (mg/dL) 145 ± 4 145 ± 6 Plasma sodium level (mEq/L) 290 ± 9 299 ± 6 Plasma osmolality (mOsm/kg)
Group OJ (n = 17)
Group SO (n = 20)
p
148 ± 37 198 ± 88 -50 ± 56 -12 ± 3 12.4 ± 9 12.1 ± 9 1.5 ± 1.2
226 ± 40 181 ± 15 45 ± 61 -4.8 ± 4 6.7 ± 5 175 ± 38 22 ± 4
0.004 NS 0.002 0.002 0.06 0.0001 0.0001
p 0.0008 NS 0.0001 0.05 0.06 NS 0.0001 NS NS
* Water intake minus urine output without taking into account insensible losses.
after laparotomy, extracellular fluid-regulating hormone plasma concentrations were higher in group OJ, except those for PRA (Table 5). Atrial natriuretic peptide plasma concentration was increased fourfold in jaundiced rabbits. At 72 hours, plasma concentrations of all hormones were again higher in group OJ (Table 5).
Effect of Water and Chow Restriction Group S02 exhibited a metabolic profile similar to that of group OJ (Tables 6, 7, and 8). In this group, however, ANP was subnormal and there was a lower activation of the PRA-aldosterone axis, suggesting that plasma volume was better maintained. Venous Sampling The results of a multiple venous sampling for ANP, carried out 1 day after common bile duct ligation in five rabbits, are shown in Figure 2. The highest concentrations of ANP were found in the aorta. There were no significant
Water intake (mL) Diuresis (mL) Water balance (mL)* Weight loss (%) Urinary sodium (mEq) Chow intake (g) Sodium intake (mEq)
* Water intake minus urine output without taking into account insensible losses.
ANP plasma concentration gradients between the portal vein and the suprahepatic veins. The results suggest that ANP was of cardiac and not of hepatic origin.
Discussion The current study shows that significant metabolic and endocrine alterations are detectable shortly after common bile duct ligation in the rabbit and gives further support to investigations linking impaired renal function with water and sodium metabolism derangements in obstructive jaundice. Persistently negative water and sodium balances, starting immediately after common bile duct ligation, were found, accounting for most of the weight loss seen in the early phases of obstructive jaundice. This basically confirms our previous findings7 and again suggests that water depletion in this model is the result of hypodipsia and loss of chow (sodium) appetite. The current study gives further information on the pathogenesis of extracellular volume depletion in obstructive jaundice. Subtle alterations in renal function
300
250
TABLE 3. Water and Sodium Metabolism Parameters 72 Hours After Common Bile Duct Ligation (Group OJ) or Sham Operation (Group SO)
Group OJ
(n = 17)
Group SO (n = 20)
Water intake (mL) 56 ± 30 93 ± 29 Diuresis (mL) 49 ± 38 59 ± 40 Water balance (mL)* 4 ± 30 18 ± 20 Weight loss (%) -9.8 ± 1.7 -5.6 ± 4.7 Urinary sodium (mEq) 1.5 ± 0.6 1.6 ± 1.1 Free water clearance (mL/min) -0. 17 ± .13 -0.17 ± .09 Total bilirubin level (mg/dL) 3.4 ± 1.6 0.2 ± 0.09 Plasma sodium level (mEq/L) 143 ± 4 142 ± 6 Plasma osmolality (mOsm/kg) 286 ± 8 285 ± 6 Plasma glucose level (mg/dL) 88 ± 10 100 ± 10
0
E
150 0
100
p 0.004 NS 0.001 0.01 NS NS 0.0001 NS NS 0.02
Water intake minus urine output without taking into account insensible losses. *
0
200
m1
50
3 -50
-100 r2
-150
-4
=0.75 0
p'0.O001
-2
2
4 %
6
8
10
12
14
16
Weight Reduction
FIG. 1. Correlation between 4 days cumulative water balance and weight loss (expressed as percentage of preoperative weight) in rabbits in both experimental groups. 0, group OJ; 0, group SO.
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557
ATRIAL NATRIURETIC PEPTIDE IN EXPERIMENTAL OBSTRUCTIVE JAUNDICE
TABLE 5. ANP, Aldosterone, ADH, and PRA Plasma Concentrations at 24 and 72 Hours After Common Bile Duct Ligation (Group OJ) or Sham Operation (Group SO) 24 hr
ANP (fmol/mL)
Aldosterone (ng/dL) ADH (pg/mL) PRA (ng/dL)
72 hr
Group OJ
Group SO
p
Group OJ
Group SO
p
41 ± 7 14.5 ± 5 21.8 ± 7 7.4 ± 5
10.7 ± 2 3.6 ± 3 12.3 ± 6 7.8 ± 7
0.0001 0.001 0.008 NS
28.4 ± 5 18.6 ± 9 25.8 ± 8 12 ± 5
11.6 ± 3 2.6 ± 1 9.3 ± 7 3 ± 1.6
0.02 0.002 0.009 0.003
were responsible for the fact that, despite the reduced water and sodium intakes observed in group OJ, the cumulative 4-day diuresis was similar in both experimental groups. Jaundiced rabbits apparently showed an impairment of the water- and salt-retaining mechanisms: at 24 hours, natriuresis was increased in group OJ and the urinary losses ofsodium over 4 days were almost twofold in group OJ compared with group SO. These findings could be explained by the concomitant increased ANP plasma concentrations because this hormone has been found to promote diuresis and natriuresis, inhibit the action of water- and sodium-retaining hormones,9 and, as previously discussed,7 may inhibit the thirst mechanism. Sodium losses similar to those observed in group OJ were found in pair-fed pair-watered animals exhibiting normal plasma ANP levels, however, suggesting that fasting and concomitant ketonuria may be the main drive to increased natriuresis. The presence of increased plasma levels of ANP also helps in the interpretation of some classic observations made by authors investigating cardiovascular alterations and renal impairment in obstructive jaundice. Williams et al.'0 emphasized the hemodynamic instability and reduced renal tolerance to hypotension seen in jaundiced patients. Saline loads do not increase blood pressure
TABLE 6. Water and Sodium Metabolism Parameters 24 Hours After Common Bile Duct Ligation (Group OJ) or Sham Operation in Pair-fed Pair-watered Rabbits (Group S02)
Weight loss (%) Diuresis (mL) Plasma sodium (mEq/L) Urinary sodium
(mEq)
Group OJ (n= 17)
Group S02 (n= 13)
p
-5.1 ± 1
-4.5 ± 2 73 ± 33
NS NS
58 ± 30 145 ± 4
142 ± 1
0.04
6±5
5.1 ± 4
NS
290 ± 9
284 ± 3
NS
Plasma osmolality
(mOsm/kg) Free water clearance (mL/min) ANP (fmol/mL) Aldosterone (ng/dL) ADH (pg/mL) PRA (ng/dL)
-0.08 41 14.5 21.8 7.4
± .03 ±7 ±5 ±7 ±5
-0.05 6.7 8.3 28.5 8.8
± .04 ±3 ± 6.5 ±7 ±8
NS 0.0001 NS 0.04 NS
in jaundiced rabbits compared with sham-operated controls. Bloom et al.'2 found that isolated renal arteries were less sensitive to norepinephrine when perfused with jaundiced plasma and postulated the presence of a plasma humoral factor counteracting the vasoconstrictive effects of the catecholamines on the renal arteries. According to our findings, these phenomena now can be explained by an elevated plasma concentrations of ANP, which leads to volume depletion and peripheral vasodilation.9 There is an ongoing controversy regarding how the "jaundiced kidney" handles sodium loads." Topuzlu and Stahl'3 were the first to show that an intravenous infusion of bile increases diuresis and natriuresis. The increased natriuresis seen in jaundiced animals is also pronounced when they are given normal saline because even in this circumstance they show a tendency toward negative sodium balance.'4 Some investigators have found that sodium handling is normal or that retention rather than sodium diuresis is a hallmark of obstructive jaundice. These studies, however, have used rat models in which bile duct obstruction is followed by ascites,'5 or have focused in the late phases (10 days) of obstructive jaundice in the rabbit," when, according to our data,6 marked volume depletion is present and sodium-retaining mechanisms may override the actions of ANP. Thus, urinary sodium excretion in ob"
TABLE 7. Water and Sodium Metabolism Parameters 72 Hours After Common Bile Duct Ligation (Group OJ) or Sham Operation in Pair-fed Pair-watered Rabbits (Group S02)
Weight loss (%) Diuresis (mL) Plasma sodium level (mEq/L) Urinary sodium level (mEq) Plasma osmolality (mOsm/kg) Free water clearance ANP (fmol/mL) Aldosterone (ng/dL) ADH (pg/mL) PRA (ng/dL)
Group OJ (n= 17)
Group S02 (n= 13)
p
-9.8 ± 2 40 ± 39
-9.4 ± 2 43 ± 43
NS NS
143 ± 4
142 ± 2
NS
1.7 ± 1.5
3.7 ± 2.6
286 ± 9 -0.17 ± .13 28.4 ± 5
285 ± 6 -0.10 ± .05 4.9 ± 2 7.5 ± 6.5 35 ± 14 9± 5
18.6 ± 5 25.8 ± 8 12 ± 5
0.04
NS NS 0.0002 0.01 NS NS
VALVERDE AND OTHERS
558
structive jaundice is dependent on both the model used and the timing of the investigation. Levy and Finestone'6 have confirmed the natriuretic and diuretic effects of shortterm bile duct obstruction in the dog. Because this physiologic effect could be transferred by cross-circulation to dogs without bile duct obstruction, these authors postulated the existence of a biliary humoral factor with a diuretic activity. On the basis of our findings, the obvious candidate for such humoral factor would be ANP. We have not found a clear-cut natriuretic effect of ANP, however, because fasted animals with subnormal plasma levels of this peptide also showed a higher natriuretic response than controls fed ad libitum. Whether ANP plays a significant role in the pathogenesis of hypodipsia and hypophagia after common bile duct ligation remains to be elucidated. The increased plasma levels of PRA, aldosterone, and ADH observed in the Group OJ may be accounted for by a falling extracellular volume. In fact, water- and sodium-restricted sham-operated controls also showed an increase in these hormones when compared with controls fed ad libitum. However, PRA and aldosteron changes were less significant in group S02 than in group OJ, suggesting that plasma volume was better controlled in shamoperated animals. Elevated plasma concentrations of aldosterone and PRA have previously been described in jaundiced animals, 11"17 although their relationship to water and sodium balances or extracellular volume were not appropriately studied. The source of increased plasma concentrations of ANP was investigated by multiple venous sampling. The highest ANP plasma concentrations were found in the aorta and infrarenal vena cava, suggesting that ANP was being released in higher amounts by the heart. The lower concentrations found in the suprahepatic veins and the absence of a concentration gradient between the portal vein and the suprahepatic veins suggests that there was no hepatic production of ANP. Thus, there seems to be a mechanism linking biliovenous regurgitation and increased ANP secretion by the heart. Green et al.'8 have TABLE 8. Cumulative Balances 4 Days After Common Bile Duct
Ligation (Group OJ) or Sham Operation (Group 502)
Ann. Surg. * November 1992
Ti
FiG. 2. Results ofmultiple venous and aortic sampling for atrial natriuretic peptide in five rabbits 24 hours after common bile duct ligation. Results are expressed in fmol/mL (mean ± SD).
demonstrated a reduction of cardiac performance in a canine model of coledocho-caval fistula. These authors showed a reduced rate of increase of left ventricular pressure that, if also present in our model, could lead to atrial stretch and increased release of ANP; however, they were unable to demonstrate ultrastructural changes in the left ventricular myocardium.'9 Evidence for an abnormal myocardial function in obstructive jaundice has been provided also by Heidenreich et al.,20 who found less mitochondria in the heart muscle of jaundiced rats and a reduction of adenosine triphosphate synthesis. Thus, although the heart status in obstructive jaundice needs further study, there is increasing evidence that bile duct obstruction may lead to a hepatocardiac syndrome. Renal function would be influenced initially by fasting or an increase in ANP plasma levels, and thereafter by a falling extracellular volume, provoking an increase of the counterregulatory sodium- and water-retaining hormones.
Group OJ (n= 17)
Group S02 (n= 13)
p
148 ± 37 198 ± 88 -50 ± 56 -12 ± 3 12.4 ± 9 12.1 ± 9 1.5 ± 1.2
150 ± 0 207 ± 40 -57 ± 40 -11.7 ± 2 11.1 ± 4 12 ± 0 1.5 ± 0
NS NS NS NS NS NS NS
The authors thank Dr. F. Echevarne's laboratory staff for their care in performing the biochemical determinations used for the study of renal function.
Water intake minus urine output without taking into account insensible losses.
1. Dawson JL. Jaundice and anoxic renal damage: protective effect of mannitol. Br Med J 1964; 1:810-81 1.
Water intake (mL)
Diuresis(mL) Water balance (mL)* Weight loss (%) Urinary sodium level (mEq) Chow intake (g) Sodium intake (mEq) *
Acknowledgment
References
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2. Allison MEM, Prentice CRM, Kennedy AC, Blumgart LH. Renal function and other factors in obstructive jaundice. Br J Surg 1979; 66:392-397. 3. Cahill CJ. Prevention of postoperative renal failure in patients with obstructive jaundice: the role of bile salts. Br J Surg 1983; 70: 590-595.
4. Thompson JN, Cohen J, Blenkharn JI, et al. A randomized clinical trial of oral ursodeoxycholic acid in obstructive jaundice. Br J Surg 1986; 73:634-636. 5. Gubern JM, Sancho JJ, Simo J, Sitges-Serra A. A randomized trial on the effect of mannitol on postoperative renal function in patients with obstructive jaundice. Surgery 1988; 103:39-44. 6. Martinez-R6denas F, Oms LM, Carulla X, et al. Measurements of body water compartments after ligation ofthe common bile duct in the rabbit. Br J Surg 1989; 76:462-464. 7. Oms L, Martinez-R6denas F, Valverde J, et al. Reduced water and sodium intakes associated with high levels of natriuretic factor following common bile duct ligation in the rabbit. Br J Surg 1990; 77:752-755. 8. Gines P, Jimenez W, Arroyo V, et al. Atrial natriuretic factor in cirrhosis with ascites: plasma levels, cardiac release and splanchnic extraction. Hepatology 1988; 8:636-642. 9. Cogan MG. Atrial natriuretic peptide. Kidney Int 1990; 37:11481160. 10. Williams RD, Elliot DW, Zollinger RM. The effect of hypotension in obstructive jaundice. Arch Surg 1960; 81:334-340. 11. Hishida A, Honda N, Sudo M, et al. Renal handling of salt and
559
water in the early stage ofobstructive jaundice in rabbits. Nephron
1982; 30:368-373. 12. Bloom DS, Eidelman BH, McCalden TA. Effects ofjaundiced plasma on vascular sensitivity to noradrenaline. Kidney Int 1975; 8:149157. 13. Topuzlu C, Stahl WM. Effect of bile infusion on the dog kidney. N Engl J Med 1966; 274:760-763. 14. Elias AN, Hoefs J, Parker L, et al. Effect of short-term bile duct ligation on peripheral blood steroids urinary PGE2 and the rate of sodium excretion in male rabbits. Gen Pharmacol 1984; 15: 427-430. 15. Yarger WE, Schrader NW, Boyd MA. Intrarenal mechanisms ofsalt retention after bile duct ligation in rats. J Clin Invest 1976; 57: 408-418. 16. Levy M, Finestone H. Renal response to four hours of biliary obstruction in the dog. Am J Physiol 1983; 244:F516-525. 17. Uemura M, Fukui H, Takaya A. Urinary prostaglandins and renal function in obstructive jaundice. Scand J Gastroenterol 1989; 24:705-715. 18. Green JM, Beyar R, Sideman S, et al. The jaundiced heart: A possible explanation for postoperative shock in obstructive jaundice. Surgery 1986; 100:1: 14-20. 19. Ludatscher RM, Binah 0, Bomzon A, et al. Ultraestructure of the myocardium in dogs with induced jaundice. Acta Anat (Basel) 1987; 130:242-246. 20. Heidenreich S, Brinkema E, Martin A, et al. The kidney and cardiovascular system in obstructive jaundice: functional and metabolic studies in conscious rats. Clin Sci 1987; 73:593-599.
