Dopamine increases renal oxygenation: a clinical study in post‐cardiac surgery patients

Background: Imbalance of the renal medullary oxygen supply/demand relationship can cause ischaemic acute renal failure (ARF). The use of dopamine for prevention/treatment of ischaemic ARF has been questioned. It has been suggested that dopamine may increase renal oxygen consumption (RVO₂) due to increased solute delivery to tubular cells, which may jeopardise renal oxygenation. Information on the effects of dopamine on renal perfusion, filtration and oxygenation in man is, however, lacking. We evaluated the effects of dopamine on renal blood flow (RBF), glomerular filtration rate (GFR), RVO₂ and renal O₂ demand/supply relationship, i.e. renal oxygen extraction (RO₂Ex). Methods: Twelve uncomplicated, mechanically ventilated and sedated post‐cardiac surgery patients with pre‐operatively normal renal function were studied. Dopamine was sequentially infused at 2 and 4 ug/kg/min. Systemic haemodynamics were evaluated by a pulmonary artery catheter. Absolute RBF was measured using two independent techniques: by the renal vein thermodilution technique and by infusion clearance of paraaminohippuric acid (PAH), with a correction for renal extraction of PAH. The filtration fraction (FF) was measured by the renal extraction of ⁵¹Cr‐EDTA. Results: Neither GFR, tubular sodium reabsorption nor RVO₂ was affected by dopamine, which increased RBF (45–55%) with both methods, decreased renal vascular resistance (30–35%), FF (21–26%) and RO₂Ex (28–34%). The RBF/CI ratio increased with dopamine. Dopamine decreased renal PAH extraction, suggestive of a flow distribution to the medulla. Conclusions: In post‐cardiac surgery patients, dopamine increases the renal oxygenation by a pronounced renal pre‐and post‐glomerular vasodilation with no increases in GFR, tubular sodium reabsorption or renal oxygen consumption.     

Low-dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post-cardiac surgery patients

Background: The beneficial effects of vasopressin on diuresis and creatinine clearance have been demonstrated when used as an additional/alternative therapy in catecholamine‐dependent vasodilatory shock. A detailed analysis of the effects of vasopressin on renal perfusion, glomerular filtration, excretory function and oxygenation in man is, however, lacking. The objective of this pharmacodynamic study was to evaluate the effects of low to moderate doses of vasopressin on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO₂) and renal oxygen extraction (RO₂Ex) in post‐cardiac surgery patients. Methods: Twelve patients were studied during sedation and mechanical ventilation after cardiac surgery. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h. At each infusion rate, systemic haemodynamics were evaluated by a pulmonary artery catheter, and RBF and GFR were measured by the renal vein thermodilution technique and by renal extraction of ⁵¹chromium–ethylenediaminetetraacetic acid, respectively. RVO₂ and RO₂Ex were calculated by arterial and renal vein blood samples. Results: The mean arterial pressure was not affected by vasopressin while cardiac output and heart rate decreased. RBF decreased and GFR, filtration fraction, sodium reabsorption, RVO₂, RO₂Ex and renal vascular resistance increased dose‐dependently with vasopressin. Vasopressin exerted direct antidiuretic and antinatriuretic effects. Conclusions: Short‐term infusion of low to moderate, non‐hypertensive doses of vasopressin induced a post‐glomerular renal vasoconstriction with a decrease in RBF and an increase in GFR in post‐cardiac surgery patients. This was accompanied by an increase in RVO₂, as a consequence of the increases in the filtered tubular load of sodium. Finally, vasopressin impaired the renal oxygen demand/supply relationship.     

Renal hemodynamics during separate and combined infusion of amino acids and dopamine

Healthy volunteers (N = 9) and patients with varying degrees of renal insufficiency (N = 36) were given a low dose of dopamine and/or amino acids intravenously during a simultaneous measurement of the glomerular filtration rate and the effective renal plasma flow. Dopamine infusion led to a rise in the glomerular filtration rate and a fall in the filtration fraction. Infusion of amino acids was accompanied by an increase in the glomerular filtration rate while the filtration fraction remained unchanged or increased slightly. The highest values for the glomerular filtration were obtained during the combined infusion of amino acids and dopamine. A reserve in filtration capacity was not or hardly present in patients with moderate (GFR 30 to 90 mliter/min/1.73 M2) to severe (GFR less than 30 mliter/min/1.73 M2) renal insufficiency. We conclude that dopamine decreases total renal vascular resistance while amino acids mainly reduce the tone of afferent arterioles. As amino acids and dopamine seem to be additive in their effects on the glomerular filtration rate, we recommend the combined infusion of these two stimuli to measure renal reserve filtration capacity.     

Proximal tubular function and hyperfiltration during amino acid infusion in man

The relations between renal hemodynamics (Inutest, CPAH) and sodium segmental handling (sodium distal delivery, distal reabsorption, and fractional excretion) were studied in 9 healthy adults infused with an isotonic amino acid solution and in 6 subjects infused with 0.9% saline for 3 h at 0.2 ml/min/kg. During all tests maximal water diuresis was induced and maintained to effect analysis of sodium segmental transport. Both types of infusion produced a similar expansion of extracellular volume (weight increase, hematocrit fall, suppressed plasma renin activity and plasma aldosterone). The amino acid infusion increased the glomerular filtration rate (GFR) and renal blood flow without modifying the filtration fraction. With saline no hemodynamic modifications were observed. The expansion with saline depressed proximal and distal sodium reabsorption whereas during amino acid infusion sodium distal delivery was unaltered and the significantly increased sodium fractional excretion was sustained only by depressed distal reabsorption. Therefore, in parallel with the GFR increase, closely dependent on renal vasodilatation, the well-known stimulation of sodium cotransport by amino acids is able to antagonize the effects of expansion on the proximal sodium reabsorption. An explanation of glomerular hyperfiltration based on a primary metabolic stimulation of the proximal tubular function is suggested.     

The response of GFR to amino acids differs between autosomal dominant polycystic kidney disease (ADPKD) and glomerular disease.

We compared the glomerular filtration rate (GFR) response to amino acids in patients with glomerular disease and polycystic kidney disease. The GFR response to infusion of amino acids (75 g/12 h), of dopamine (2 micrograms/kg per min), or their combination was evaluated in nine healthy probands and in patients with two types of renal diseases at various degrees of renal function: 15 patients with ADPKD and 11 patients with glomerular disease (IgA glomerulonephritis or diabetic nephropathy). Steady-state inulin infusion technique was used. In healthy subjects amino acids increased median C(in) in response to amino acids was not found in glomerular disease. In contrast in most ADPKD patients median C(in) increased after amino acids (+6.0 ml/min; range -4 to +68), (P less than 0.05). The response to amino acids was not modified by dopamine. The results demonstrate that amino acid-induced acute changes of glomerular filtration differ in polycystic kidney disease compared with glomerular disease. These observations may have implications with respect to mechanisms of progression.     

Testing renal reserve filtration capacity with an amino acid solution

In healthy individuals and in patients with varying degrees of impaired renal function, glomerular filtration rate (GFR) and effective renal plasma flow were measured before and during infusion of an amino acid solution (Vamin N). GFR increased during amino acid infusion in healthy individuals while the filtration fraction (FF) remained constant. However, in patients with impaired renal function no significant changes in GFR were observed. The FF increased slightly. We conclude that amino acid infusion can increase GFR, possibly by utilization of 'dormant cortical nephrons' together with a rise in net ultrafiltration pressure of other filtrating glomeruli, both due to afferent vasodilatation. Thus, amino acid administration can be used to test the presence of reserve filtration capacity.     

Renal hypoxanthine balance in cardiac surgery: effects of felodipine

OBJECTIVE: To test the hypothesis that felodipine, a renal vasodilator, can prevent a release of hypoxanthine during rewarming after moderate hypothermic cardiopulmonary bypass and that this is related to improved renal oxygen supply. DESIGN: A prospective, randomized, and controlled study. SETTING: Operating room in the cardiothoracic surgery department of a university hospital. PARTICIPANTS: Twenty-two patients submitted to elective first-time coronary bypass surgery. INTERVENTIONS: A catheter was placed in the left renal vein for thermodilution renal blood flow (RBF) measurement and blood sampling. In 11 patients, felodipine was infused during the hypothermic period of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Renal uptake (renal arteriovenous concentration difference x RBF) of hypoxanthine was maintained during rewarming in felodipine-treated patients but not in control patients (55+/-28 v. -39+/-1 nmol/min, p<0.05). Oxygen consumption was higher after felodipine infusion despite unchanged total RBF. A positive correlation between renal oxygen consumption and hypoxanthine uptake and release (r = 0.74, p<0.01) was observed. CONCLUSIONS: Felodipine maintained renal uptake of hypoxanthine during rewarming after hypothermic cardiopulmonary bypass. This maintenance is the effect of improved renal oxygen supply secondary to improved nutritive blood flow at the expense of nonnutritive renal blood flow.     

Abnormal renal vasodilation to an amino acid infusion in congestive heart failure: normalization by enalapril

In congestive heart failure (CHF), the neurohormonal mechanisms that cause renal vasoconstriction, particularly those depending on the renin-angiotensin system, could interfere with renal vasodilating mechanisms. To elucidate this issue, we studied the kidney response to an amino acid infusion (known to cause renal vasodilation in healthy individuals) in eight patients with CHF. We found that the amino acid infusion (0.7 mL/kg/h of a 10% solution) elicited no renal hemodynamic response, in marked contrast to healthy subjects. We next hypothesized that the renin-angiotensin system (known to be activated in heart failure) has a role in the lack of response to the amino acid infusion. To test this hypothesis, we repeated the study after two 5-mg doses of enalapril, an inhibitor of the angiotensin-converting enzyme, administered 12 hours apart. After enalapril treatment, the amino acid infusion caused a 45% increase in mean renal blood flow (RBF) from 383 +/- 55 to 557 +/- 51 mL/min at the fifth hour (P < 0.05). This normalization of the renal response to the amino acid infusion occurred without changes in cardiac output or in systemic vascular resistance. Hence, the renal fraction of the cardiac output increased during the amino acid infusion. The recovery of the renal vascular response was not accompanied by an increase in glomerular filtration rate (GFR; filtration fraction decreased), suggesting a predominant efferent arteriole dilatation. Our study shows that, in heart failure, the kidney loses its ability to increase RBF in response to an amino acid load. This lack of renal vascular response can be restored by inhibiting the renin-angiotensin system and is unrelated to changes in systemic hemodynamics.     

Long-term infusion of atrial natriuretic peptide (ANP) improves renal blood flow and glomerular filtration rate in clinical acute renal failure

BACKGROUND: Short-term infusion of atrial natriuretic peptide (ANP) increases renal blood flow (RBF) and glomerular filtration rate (GFR) in patients with acute renal dysfunction. In the present study we evaluated the effects of long-term infusion (>48 h) of ANP on (RBF) and (GFR) in 11 postcardiac surgical patients requiring pharmacological circulatory support and with acute renal impairment. METHODS: Urinary clearance of Cr-EDTA and PAH as well as central hemodynamic measurements were performed for 2-3 consecutive 30-min periods during ANP infusion (50 ng. kg-1. min-1), one hour after abrupt discontinuation of ANP and again immediately after reinstitution of ANP infusion. RESULTS: During ANP infusion, urine flow (UF), GFR, RBF and renal vascular resistance (RVR) were 6.4+/-1.1 ml. min-1, 19.9+/-3.1 ml. min-1, 408+/-108 ml. min-1 and 0.286+/-0.054 mmHg. min. ml-1, respectively. UF, GFR and RBF decreased significantly by 28% (P<0.001), 32% (P<0.01) and 31% (P<0.05), respectively when ANP infusion was discontinued. RVR increased by 93% (P<0.05) while there was no change in filtration fraction. After reinstitution of ANP infusion, all measured renal variables returned to baseline. There was no significant correlation between the number of ANP treatment days and the percentage decrease in GFR (r=0.18) or RBF (r=0.22) during ANP withdrawal. Central hemodynamic variables were not affected by ANP withdrawal. CONCLUSIONS: ANP infusion improves RBF and GFR in patients with acute renal impairment after cardiac surgery. This renal vasodilatory effect is maintained during a long-term infusion and seems to be hemodynamically safe.     

The amino acid-induced alteration in renal hemodynamics is glucagon independent

The amino acid-induced alteration in renal hemodynamics is glucagon independent. An oral protein load or i.v. administration of an amino acid solution results in an increase in glomerular filtration rate and renal plasma flow in both humans and animals. The change in renal hemodynamics has been attributed to the simultaneous induced rise in glucagon. Whether glucagon is necessary for the change in renal hemodynamics after an amino acid infusion was investigated. Two groups of dogs were used, and the experimental protocol was divided into four different periods (P1 through P4). Group I animals received an amino acid solution, and group II dogs received an equiosmolar solution of mannitol. In P1, the animals in both groups were hydrated with normal saline, whereas, in P2, the pancreatic clamp technique was used to fix the plasma glucagon levels. P2 served as a basal period in which measurements of glomerular filtration rate, renal plasma flow, and plasma glucagon were obtained. IN P3, group I animals received amino acid solution, and group II received mannitol and served as controls. In this period, an increase of 32 and 27% in glomerular filtration rate and renal plasma flow, respectively, in group I dogs was observed, whereas there were no significant changes in these parameters in group II. During this period, plasma glucagon remained still at basal level in both groups. In P4, an infusion of glucagon at a rate of 5 ng/kg/min was added to both groups. This maneuver resulted in a fourfold increase in plasma glucagon levels in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Erythropoietin does not attenuate renal dysfunction or inflammation in a porcine model of endotoxemia

Background: Erythropoietin (EPO) is a multifunctional cytokine with anti‐apoptotic, anti‐inflammatory, and organ protective effects. EPO protects against ischemia–reperfusion injuries, and recent reports suggest that EPO also prevents organ dysfunction in experimental sepsis. The aims of this study were to determine whether EPO prevents endotoxemia‐induced organ dysfunction in a porcine model and to characterize the immunomodulatory and anti‐apoptotic effects of EPO. Methods: Twenty‐eight pigs were randomly assigned to three groups: (1) endotoxemia treated with EPO 5000 IU/kg, (2) endotoxemia treated with placebo, and (3) a sham group anesthetized and submitted to sham operation without treatment. A laparotomy was performed, and a flow probe was placed around the left renal artery, which allowed renal blood flow (RBF) measurements. Endotoxemia was induced by an infusion of lipopolysaccharide. After 2 h, the infusion was reduced to a maintenance dose and the animals were fluid resuscitated. The glomerular filtration rate (GFR), RBF, renal oxygen consumption, and plasma cytokines [interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, and tumor necrosis factor‐alpha] were analyzed. Renal biopsies were analyzed for cytokine content and apoptosis. Results: Endotoxemia elicited impaired renal function, estimated as GFR, and increased the levels of renal apoptotic cells, with no modifying effect of EPO. Furthermore, EPO had no effect on RBF, renal oxygen consumption, or the systemic hemodynamic response to endotoxemia. EPO did not modify the inflammatory response, measured as changes in cytokine levels in plasma and organs. Conclusion: EPO did not confer renal protection in this fluid‐resuscitated porcine model of endotoxemia, and EPO did not modify the inflammatory response.     

Preoperative inhibition of angiotensin-converting enzyme improves systemic and renal haemodynamic changes during aortic abdominal surgery

We studied 22 patients undergoing aortic surgery, allocated randomly to receive, before induction of anaesthesia, a single i.v. dose of enalapril 50 micrograms kg-1 or saline. During infrarenal aortic cross- clamping, we observed similar reductions in oxygen uptake in the two groups, despite greater systemic oxygen delivery in enalapril-treated patients; angiotensin-converting enzyme inhibition prevented the reduction in cardiac output and attenuated the decrease in glomerular filtration. Changes in glomerular filtration secondary to aortic clamping were related positively to changes in renal plasma flow (r = 0.83 (saline group) and r = 0.65 (enalapril group)). Creatinine clearance on the first day after operation was significantly higher in the enalapril compared with the saline group. We conclude that enalapril pretreatment is effective in improving systemic oxygen delivery, renal plasma flow and glomerular filtration during aortic abdominal surgery.      

Kidney hemodynamics after ketone body and amino acid infusion in normal and IDDM subjects

Little information is available on the hemodynamic response (renal reserve) of the diabetic kidney during an acute amino acid infusion, which has been shown to increase glomerular filtration rate (GFR) in normal humans. We recently found that the infusion of ketone bodies is able to raise GFR in both normal subjects and insulin-dependent diabetes mellitus (IDDM) patients. The aim of this study was to evaluate the renal reserve in 15 IDDM patients with a duration of diabetes of greater than 9 yr [8 with albumin excretion rate less than 15 micrograms/min (group 1) and 7 with albumin excretion rate greater than 100 micrograms/min (group 2)] and in 8 normal subjects during amino acid infusion (33 mumol.kg-1.min-1, Travasol 10% wt/vol solution containing 0.154 mM sodium chloride concentration; Travenol, Savage, MD) and during acetoacetic sodium salt (25 mumol.kg-1.min-1) infusion. Blood glucose was clamped at euglycemic levels. The infusion of sodium acetoacetate resulted in a 10- to 15-fold increase in circulating concentrations of ketone bodies, which were similar in magnitude in normal subjects and diabetic patients. The GFR peak increase above baseline after sodium acetoacetate infusion was 28% in normal subjects and 27% in group 1 and 19% in group 2 diabetic patients. The infusion of amino acid solution produced a three- to fivefold increase in plasma concentrations of amino acids in both normal subjects and diabetic patients. The GFR peak increase above baseline after amino acid infusion was significantly lower in diabetic patients (IDDM group 1: 5%, P less than .01; IDDM group 2: 6%, P less than .01) than in normal subjects (38%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of nifedipine and captopril on glomerular hyperfiltration in normotensive man.

Glomerular hyperfiltration and hypertension induced by extensive loss of renal parenchyma are suspected to accelerate progression of renal failure. Amino acid infusion or protein ingestion also modify renal hemodynamics and increase glomerular filtration rate (GFR). This phenomenon was used to study the influence of two commonly used antihypertensive agents, captopril and nifedipine, on renal hemodynamics at rest and during glomerular hyperfiltration. Thirteen healthy volunteers were studied on three separate days (days A, B, and C) in random sequence: inulin and p-amino hippurate (PAH) clearance were measured first under glucose infusion and afterwards under stimulation by amino acid infusion (0.35 mmol/kg/min; 4 mg/kg/min). Day A served as a control, where no medication was given. On day B, 10 mg nifedipine, and on day C, 25 mg captopril, were administered orally before study. Without premedication (= day A, control) GFR increased from 108.0 +/- 6.9 mL/min (SEM) to 131.7 +/- 7.0 mL/min (P less than 0.05). On day B (nifedipine), GFR before stimulation by amino acids was already elevated to 121.8 +/- 4.2 mL/min (P less than 0.05 compared with day A) and increased to 132.6 +/- 6.3 mL/min with infusion of amino acids, thus to the same range as on day A without medication. On day C, after captopril, GFR did not increase with infusion of amino acids (from 112.5 +/- 7.2 to 117.3 +/- 6.3 mL/min). Our results indicate the calcium channel antagonist nifedipine and the angiotensin-converting enzyme (ACE) inhibitor captopril differ in their effect on intrarenal hemodynamic parameters. Nifedipine induces hyperfiltration at rest and allows maximal hyperfiltration to develop under amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal vasoconstriction in association with acute pancreatitis

Renal failure is a common complication of pancreatitis. To better understand this association, renal function was evaluated in eleven patients in the acute phase of alcoholic pancreatitis and again during convalescence in seven patients. Parameters measured included glomerular filtration rate, effective renal plasma flow, true renal plasma flow, renal vascular resistance, osmolar clearance, amylase clearance, renal oxygen consumption, cardiac output, and peripheral resistance.Average glomerular filtration rate, effective renal plasma flow, and true renal plasma flow were decreased in the acute phase. Osmolar clearance, amylase clearance, mean arterial blood pressure, renal vascular resistance, and total peripheral resistance rose in the acute phase. Cardiac index and extracellular fluid space remained normal. All parameters returned toward normal with convalescence.The combination of systemic hypertension, increased total peripheral resistance and renal vascular resistance, and normal extracellular fluid space suggests a release of a vasopressor during the acute phase of pancreatitis. The therapeutic implications of these findings including the role of vasodilator infusion are discussed.     

Influence of a low sodium diet on the renal response to amino acid infusions in humans

In experimental animals, a high protein diet has been shown to accelerate end-stage renal disease by inducing glomerular hyperperfusion. In this study, we found that intravenous administration of amino acid, used as one component of parenteral nutrition, to normal volunteers resulted in a significant increase in renal blood flow (from 517 +/- 29 to 754 +/- 60 ml/min) and glomerular filtration rate (from 106 +/- 6 to 165 +/- 12 ml/min) without altering systemic blood pressure, renal excretion of electrolytes, plasma renin activity, or plasma aldosterone concentration, and excretory rates of prostaglandins E2 were increased (from 665 +/- 61 to 1,034 +/- 153 pg/min). These amino acid-induced renal hemodynamic effects were abolished when the volunteers received a low sodium diet (20 mEq/day) for three days before the amino acid infusions. However, the hemodynamic effects were restored when the subjects receiving low sodium diets were pretreated with captopril. Under these conditions, amino acid infusions increased renal blood flow (from 388 +/- 11 to 597 +/- 27 ml/min) and glomerular filtration rate (from 80 +/- 4 to 118 +/- 9 ml/min). Reduction of prostaglandin synthesis with indomethacin in volunteers receiving a normal sodium intake was also capable of significantly decreasing the amino acid effects on renal hemodynamics. The results indicate that the renal hemodynamic effects of amino acid infusion are strongly influenced by angiotensin II and prostaglandin formation.     

Effect of two regimens of intravenous amino acid infusion on renal haemodynamics, renal tubular function and sodium and water homeostatic hormones in healthy humans

The effect of two different regimens of intravenous infusion of amino acids on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and water handling judged from the clearance of lithium (CLi), and plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), arginine vasopressin (AVP), atrial natriuretic peptide (ANP), growth hormone (GH), and glucagon was investigated in healthy humans. In the first protocol (n = 11) the infusion lasted 90 min; both GFR and RPF increased significantly (median increase 7.1% and 9.1% respectively, P less than 0.05 both). In the second protocol (n = 13) the infusion lasted 30 min; both GFR and RPF tended to increase (median increase 3.5% and 7.4%) but the change did not reach significance. The changes in tubular sodium and water handling were similar in the two protocols. Absolute reabsorption rates in the proximal tubules were unaltered, resulting in an increased output into the distal tubules that was totally compensated for by an increased distal reabsorption. Thus no changes in urinary excretion of sodium and water were observed. Ang II, Aldo, AVP, ANP and GH were unchanged by amino acid infusion, but glucagon increased. It is suggested that the alterations in renal haemodynamics and distal tubular reabsorption may be mediated by glucagon.     

Controlled hypotension with adenosine or sodium nitroprusside during cerebral aneurysm surgery: effects on renal hemodynamics, excretory function, and renin release

Adenosine, a potent vasodilator both in animals and in humans, has been used to produce controlled hypotension in patients, especially during cerebral aneurysm surgery. However, in animals adenosine by intrarenal infusion decreases renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and causes an inhibition of renin secretion. In this study we evaluated the effect of adenosine on RBF in patients (n = 15) scheduled for cerebral aneurysm surgery who had been anesthetized with a modified neurolept-anesthesia during controlled hyperventilation. Perioperative hypotension was achieved with infusion of adenosine (252.8 +/- 55.8 micrograms.kg-1.min-1) (n = 8) or sodium nitroprusside (2.5 +/- 0.8 micrograms.kg-1.min-1) (n = 7). Mean arterial pressure was lowered by 25%-30%, to approximately 60-70 mm Hg, in both groups. Glomerular filtration rate and RBF were measured using standard renal clearance methods for 51Cr-ethylenediaminetetraacetic acid and paraaminohippuric acid. Urine and blood samples were collected during normotension before and after a bolus dose of hypertonic mannitol, during hypotension, and during normotension after clipping of the aneurysm. Adenosine induced a marked decrease in GFR (-91%) and RBF (-92%), and a pronounced increase in renal vascular resistance. Sodium nitroprusside caused a significantly (P less than 0.01) less pronounced decrease in GFR (-24%) and RBF (-36%), but did not affect renal vascular resistance. After discontinuation of the hypotensive agents, GFR returned to baseline levels in both groups. Renal blood flow, however, increased above baseline after discontinuation of adenosine (+93%) but not after sodium nitroprusside. Sodium nitroprusside increased renin secretion, which was not seen with adenosine. Four patients in the adenosine group developed reversible atrioventricular conduction disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tubular handling of amino acids after intravenous infusion of amino acids in healthy humans.

To examine the fractional excretion of amino acids after an increase in the filtered load, and to study a possible coupling between proximal tubular reabsorption of individual amino acids and sodium/water, eleven healthy subjects were examined before and during intravenous infusion of a mixture of essential and non-essential amino acids. Thirteen healthy subjects, who received isotonic glucose instead, participated in an identical time-control study. Glomerular filtration rate (GFR), renal plasma flow (RPF), and proximal and distal absolute and fractional tubular reabsorption of sodium and water (PARNa, PFRNa/water, DARNa, and DFRNa) evaluated by the lithium clearance method were determined during four clearance periods of 30 min each. After amino acid infusion, GFR and RPF increased, whereas filtration fraction (FF) was unchanged. PARNa was unchanged, but lithium clearance increased significantly (P less than 0.05) and PFRNa/water fell, indicating an increased delivery of sodium and water out of the proximal tubules. DARNa increased, but DFRNa was unchanged, thus no net increase was recorded in urinary sodium and water output. In the time-control study, no changes in kidney function were seen. Absolute excretion of amino acids increased for glutamic acid, serine, glutamine, glycine, threonine, histidine, alanine, arginine, tyrosine, valine, methionine, isoleucine, phenylalanine, leucine, and lysine (P less than 0.01), and fractional excretion increased for all but glutamic acid, tyrosine, arginine, isoleucine, and leucine. Reabsorption of amino acids was enhanced uniformly and almost paralleled the filtered load without any sign of saturation of the reabsorption mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal hemodynamic effects of therapeutic plasma levels of sulindac sulfide during hemorrhage

There is continued debate over any renal sparing effects of sulindac (S): such a property would be of benefit and be unique among nonsteroidal anti-inflammatory drugs (NSAIDS). S undergoes a distinct metabolism whereby the active drug (sulindac sulfide (SS)) does not appear in the urine. Accordingly, we tested the effect of a plasma concentration of SS in the therapeutic range on renal blood flow (RBF), glomerular filtration rate (GFR), and renal prostaglandin (PG) concentrations during sudden renal ischemic stress. The ischemic stress was produced by a 15 to 20% reduction in arterial pressure by arterial hemorrhage (H) in four separate groups of anesthetized dogs: control, SS (0.4 mg/kg i.v. bolus followed by 0.03 mg/kg/min constant infusion), indomethacin (I, 10 mg/kg), and benoxaprofen (B, 75 mg/kg). A plasma concentration of 3.69 micrograms/ml of SS was achieved by the infusion, and no SS appeared in the urine. H reduced GFR (by 46%) and RBF (by 38%) in control dogs; in SS-treated dogs, a 60% decline in GFR and a 73% decrease in RGF occurred. These decreases in renal hemodynamics in the SS group during H were significantly greater than in the control group. Further, these decrements in GFR and RBF were similar to those observed in the I- and B-treated dogs. Finally, SS reduced baseline arterial and renal PG concentrations, and prevented any increase in renal PG release during H. Thus, we conclude that a concentration of SS in the therapeutic range, which does not appear in the urine, is capable of enhancing the decline in GFR and RBF during a sudden ischemic stress such as H.