Effects of prophylactic fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs.

OBJECTIVE: It was hypothesized that fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of fenoldopam (0.1 microg x kg(-1) x min(-1)) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. DESIGN: Prospective, randomized, controlled experiment. SETTING: University-based animal laboratory and research unit. SUBJECTS: Eight female beagle dogs. INTERVENTIONS: Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of fenoldopam or normal saline; b) during infusion of fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. MEASUREMENTS AND MAIN RESULTS: Administration of fenoldopam (0.1 microg x kg(-1) x min(-1)) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 +/- 20 to 47 +/- 6 mL/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in the fenoldopam group (75 +/- 14 to 73 +/- 17 mL/min and 0.3 +/- 0.19 to 0.14 +/- 0.05 mL/min, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 +/- 0.4 to 1.8 +/- 0.8 mL x kg(-1) x min(-1) and 1.7% +/- 0.9% to 0.4% +/- 0.2%, respectively) but not in the dogs that received fenoldopam (3.0 +/- 1.0 to 2.9 +/- 0.5 mL x kg(-1) x min(-1) and 1.9% +/- 1.1% to 1.7% +/- 2.7%, respectively). CONCLUSIONS: Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that fenoldopam may have a renoprotective effect in acute ischemic injury.

The effects of fenoldopam on renal blood flow and tubular function during aortic cross-clamping in anaesthetized dogs.

Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Fenoldopam, a selective dopamine agonist, may increase renal blood flow and decrease tubular oxygen consumption. The objective of this study was to quantify the effects of fenoldopam (0.1 microg kg-1 min-1) on renal blood flow and renal tubular function in anaesthetized dogs that have undergone aortic cross clamping. Eight labrador dogs were selected to receive either saline or fenoldopam (0.1 microg kg-1 min-1) intravenously. Arterial pressure, heart rate, renal blood flow, urinary output, fractional excretion of sodium, creatinine clearance and lithium clearance were measured (a) prior to infusions of saline or fenoldopam (b) 1 h after commencing the infusion (c) during a 90-min period of infrarenal aortic cross-clamping with concurrent infusion of fenoldopam or saline and (d) for 1 h after simultaneous aortic declamping and discontinuation of the infusions. There was no haemodynamic instability upon commencing the infusion of fenoldopam (0.1 microg kg-1 min-1). Creatinine clearance (2.03 +/- 0.5-2.45 +/- 0.3 mL min-1 kg-1 (mean +/- SD)), urine output (0.23 +/- 0.16-0.35 +/- 0.23 mL min-1 (mean +/- SD)), and fractional excretion of sodium (0.7 +/- 0.52-1.3 +/- 0.73% (mean +/- SD)) increased (P < 0.05), following commencement of the fenoldopam infusion. Fractional excretion of sodium (1.2 +/- 0.7% (mean +/- SD)) and urine output (0. 36 +/- 0.21 mL min-1 (mean +/- SD)) were maintained during the aortic cross-clamp period (P < 0.05). Renal blood flow increased when the fenoldopam infusion was commenced (145 +/- 43.3-161 +/- 39. 2 mL min-1 (mean +/- SD)) and remained greater than baseline during the aortic cross-clamping period (152 +/- 44 mL min-1 (mean +/- SD)), although these increases did not reach statistical significance. The most striking abnormalities observed by electron microscopy were marked disruption of the microvillus brush border in proximal tubules, vacuolation and separation of epithelial cells on basolateral infolds. The changes were similar in the two groups. In conclusion fenoldopam (0.1 microg kg-1 min-1) may have renoprotective effects which persist during infrarenal aortic cross clamping.

Evaluation of standard haemodynamic tests of autonomic function and HbA1c as predictors of delayed gastric emptying in patients with type 1 diabetes mellitus.

We examined the relation between chronic glycaemic control (using glycosylated haemoglobin), haemodynamic autonomic function and rate of gastric emptying in 16 patients with type 1 diabetes mellitus. Gastric emptying was measured using a paracetamol absorption technique. Parameters of gastric emptying include area under the plasma paracetamol concentration time curve. Patients were classified as diabetic autonomic neuropathy positive or negative using five standardized haemodynamic reflex tests. Area under the plasma paracetamol concentration time curve in the neuropathy positive (10.36 (4.5) mmol.-1. min) and negative (9.84 (3.0) mmol.-1. min) groups were similar (.P.=0.42) using unpaired Student's.t. -tests. Glycosylated haemoglobin concentration and area under the plasma paracetamol concentration time curve (.n.=16) demonstrated a Pearson's correlation co-efficient of 0.24. Neither tests of haemodynamic autonomic function, nor concentration of glycosylated haemoglobin, are predictive of diabetic gastroparesis.

Adaptation and validation of a radioimmunoassay kit for measuring plasma cortisol in turbot.

Levels of cortisol in fish blood provide quantitative information on the degree of stress induced by a variety of stressors. It is also useful in describing the social status of individual fish within groups. The commercial production of radioimmunoassay (RIA) kits, such as the DPC Coat-A-Count radioimmunoassay kit, has considerably reduced the effort required for cortisol measurement. These kits employ human plasma based cortisol standards which are not compatible for use with non mammalian species such as fish e.g. turbot, Scophthalmus maximus (Rafinesque), blood due to the interference effect of lipids and steroid binding proteins present in the plasma. In this study the DPC kit was used following the removal of these lipids and steroid binding proteins from the plasma using an ethanol-hexane extraction. Excessive variability in the cortisol values obtained using this method deemed it unsatisfactory in overcoming the problem of incompatibility. A second modification of this technique that was tested involved the preparation of turbot specific standards for use in the preparation of modified standard curves. Using this method, an accuracy of 93.4% was achieved, as opposed to 79.6% using the kit human plasma based standards, and 47.1% using samples following lipid removal using an ethanol-hexane extraction. Based on analysis of accuracy, precision and reproducibility it is concluded that commercially available cortisol kits are suitable for use with turbot plasma, but a number of minor modifications are necessary.

The effect of lactase and formula reconstitution on milk osmolality.

These experiments investigated the reaction rate of lactase on milk lactose by measuring milk osmolality; and explored the effect of formula reconstitution on milk osmolality. The investigations measured milk osmolality with the Fiske Os, freezing-point osmometer. Lactase (Lactaid) incubated with pure lactose solutions established the validity of the method. Lactase was incubated for 24 hours with four reconstituted milk formulas (Milumil, and Cow and Gate Nutrilon Plus, Farley's First Milk, SMA Gold). Milk osmolality increased most rapidly in the first 4 hours after the addition of lactase. The lactase enzyme completed over 90% of the reaction within 12 hours. The milk osmolalities ranged from 487 to 591 mosm/kg after 24 hours with 2-4 drops of lactase in 240 ml of formula. A clinical guideline osmolality of 400 mosm/kg was reached in 240 ml of formula at 1 to 12 hours depending on the dose of lactase. High milk osmolalities due to prolonged enzyme incubation, or high lactase doses could be reduced to around 400 mosm/kg by dilution of 240 ml of formula with an extra 60 ml of water. The initial osmolality of formula after reconstitution by paediatric nurses varied widely and usually exceeded the manufacturer's quoted osmolality. This initial osmolality was a further influence on the final osmolality reached after the addition of lactase. It is concluded that the recommended incubation time for Lactaid of 24 hours is unnecessary as lactase exerts the majority of its effect in less than 12 hours. Adjustment of Lactaid dose and incubation times will maintain milk formula osmolality within standard guidelines. Dilution with extra water will correct inadvertent high enzyme doses and prolonged incubation times. The normal method of reconstituting milk formulas from powder may be unreliable as the manufacturer's quoted osmolality was not reproduced when milk formulas were reconstituted by paediatric nurses.

Effect of anxiety on the rate of gastric emptying of liquids.

The efficacy of preoperative fasting is reduced in the presence of any factor which delays gastric emptying. We examined the association between anxiety and gastric emptying in adult patients undergoing elective surgery. Immediately before operation, 21 patients completed both a Spielberger state trait inventory (used to quantify current anxiety state (STAIs) and anxiety predisposition (STAIt)), and the Amsterdam preoperative anxiety and information scale (used to quantify anxiety and need for information). Gastric emptying was measured using the paracetamol absorption technique. Four to 10 weeks later, gastric emptying and STAI were measured again. Patients were more anxious before than after operation (STAIs = mean 35.4 (SD 10.9) and 25 (4.1), respectively; P = 0.0004). Neither anxiety state (P = 0.40) nor measures of anxiety relative to anxiety predisposition (P = 0.86) influenced gastric emptying (as measured by area under the paracetamol absorption-time curve). This contrasts with previous findings that anxiety in patients with low anxiety predisposition scores delays gastric emptying.

Elevated serum angiotensin converting enzyme levels in metastatic ovarian dysgerminoma.

A case of a 32-year-old XY genotype female is described, presenting with mediastinal and abdominal lymphadenopathy and associated with an elevated serum angiotensin I converting enzyme (SACE) level. Lymph node histology showed a malignant dysgerminoma of ovarian origin. Combined chemotherapy led to a radiological regression of the lymphadenopathy and coincided with a decrease in SACE concentration. The authors suggest that SACE may be a marker for disseminated germinoma tumours and may be useful for monitoring treatment.

Perioperative creatine phosphokinase trends in elderly patients with hip fracture.

A prospective study of the serum levels of unfractionated creatine phosphokinase (CPK) in 69 consecutive elderly patients undergoing surgery for hip fracture is reported. Serum unfractionated CPK levels were measured on admission, on the evening following surgery and daily for the first five days post-operatively. All of the CPK levels measured on admission were within the normal range for this laboratory. A gradual rise in CPK levels followed surgery. On the evening following surgery 75% of values were greater than the upper limit of the normal reference range. The peak values were seen on day 1 post-operatively but 25% of values were still less than the reference maximum. A gradual decline was seen after this and at day 5 post operatively 50% of values were within the normal reference range. A single unfractionated CPK determination is not of diagnostic benefit in the post-operative period in elderly patients with hip fracture. However, patients with intracapsular and intertrochanteric fractures do not show elevation of unfractionated CPK levels prior to surgery.

Microalbuminuria in NIDDM.

OBJECTIVE: To determine an effective screening procedure for microalbuminuria. RESEARCH DESIGN AND METHODS: The prevalence of microalbuminuria in NIDDM patients whose urine was negative on routine Albustix testing was studied. Microalbuminuria was measured in overnight urine samples from 128 NIDDM patients on at least two of three occasions over a 6-mo period. Patients were tested with Micro-Bumintest or Micral-Test. RESULTS: Ten of 128 patients had albumin concentrations > or = 20 mg/L on two or more occasions, 14 patients had A-C ratios > or = 3 mg/M on two or more occasions, and 9 patients had both. CONCLUSIONS: Neither Micro-Bumintest nor Micral-Test is a useful or feasible screening procedure for microalbuminuria.

A robust procedure for the automated measurement of total serum bilirubin using potassium ferricyanide.

Bilirubin is oxidized to biliverdin by 1.0 mmol/L potassium ferricyanide in the presence of caffeine. The absorbance decline at 480 nm with blanking at 660 nm is proportional to bilirubin concentration. The assay is linear up to 1000 mumol/L and is suitable for the measurement of bilirubin in adult and neonatal patients. The assay is accurate and precise and is not significantly affected by haemolysis up to 5.0 g/L haemoglobin. Reagents and calibration are stable for at least 3 months.

A simplified procedure for eliminating the negative interference of bilirubin in the Jaffé reaction for creatinine.

The negative interference by bilirubin in the measurement of creatinine by the Jaffé procedure is well documented. We describe a procedure for the elimination of interfering bilirubin by oxidation to biliverdin through the addition of potassium ferricyanide before the alkaline picrate reagent. We detected no negative interference with the addition of as much as 600 mumol/L bilirubin. The procedure shows good agreement with a recently described blank rate method for analyzing icteric samples.

Measuring albumin and calcium in serum in a dual test with the Hitachi 704.

We describe a method for simultaneously determining albumin, by using bromcresol purple, and calcium, by using Arsenazo III, in the same analytical cuvette on the Hitachi 704. Both assays agree well with accepted procedures. The standard curves for the albumin and calcium assays are linear from 0 to 60 g/L and 0 to 5.0 mmol/L, respectively. Calibration is stable for 7 days with use of open reagent in the instrument. Both assays are unaffected by hemoglobin less than or equal to 5 g/L and Intralipid less than or equal to 4 g/L; calcium is unaffected by bilirubin less than or equal to 600 mumol/L.

Single stable reagent (Arsenazo III) for optically robust measurement of calcium in serum and plasma.

We describe a method based on a single stable reagent for the determination of calcium in serum and plasma with use of Arsenazo III, 200 mumol/L in 50 mmol/L 1,4-piperazinediethanesulfonic acid (PIPES) buffer. The method showed significant positive interference in plasma at pH less than 6.6 because of the precipitation of fibrinogen, which was eliminated by increasing the pH to 6.8. The assay showed no interference from as much as 600 mumol of bilirubin and 12 g of hemoglobin per liter when applied in a simple monochromatic procedure at 660 nm. The standard curve for calcium was linear from 0 to 5.0 mmol/L. Addition of Intralipid at concentrations greater than 3 g/L demonstrated positive interference, which could be eliminated by using a 700-nm blanking wavelength. The procedure showed good agreement with all-method mean values from two external quality-control schemes.

Improving accuracy of glucose oxidase procedure for glucose determinations on discrete analyzers.

We describe a rapid kinetic glucose oxidase (EC 1.1.3.4) procedure for quantifying glucose. Glucose oxidase concentration was reduced from the more usual 20 kU/L to 4 kU/L, and pH was reduced from 7.0 to 6.6. Potassium ferrocyanide (20 mumol/L) and ascorbate oxidase (1 kU/L) were incorporated in the procedure. The assay results vary linearly with glucose concentration from 0 to 50 mmol/L and are unaffected by bilirubin concentrations less than or equal to 600 mumol/L, hemoglobin less than or equal to 12 g/L, Intralipid less than or equal to 4 g/L, urate less than or equal to 1 mmol/L, and ascorbate less than or equal to 2.0 mmol/L. The assay is readily adaptable to most open-system analyzers.

Adapting the uricase/peroxidase procedure for plasma urate to reduce interference due to haemolysis, icterus or lipaemia.

The estimation of serum urate by uricase/peroxidase procedures involving single point bichromatic absorbance monitoring gives inaccurate results with samples which are haemolysed, icteric or lipaemic. These inaccuracies can be greatly minimized by reducing the rate of chromogen formation and applying the assay in a kinetic mode.

Relation of angiographically defined coronary artery disease to serum lipoprotein levels.

The relationship of coronary artery disease to plasma lipoproteins was examined in 43 men admitted to our unit with suspected ischemic heart disease. Coronary arteriography was performed, and a score reflecting the severity of disease was assigned to the angiogram. Plasma, obtained after a 12-h overnight fast, was assayed for triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and HDL-3 cholesterol. HDL-2 cholesterol was found by subtraction. The cholesterol contents of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) were quantitated by the Freidwald equation. Men with high coronary scores tended to be older, and subjects with moderate coronary disease had significantly higher total and LDL cholesterol values than those with minimal disease. Age was the only factor to be significantly associated with coronary score and there was no significant association between coronary score and total LDL and HDL cholesterol or its subfractions when the age factor was taken into account.