Sodium Iothalamate Research Articles

Effect of sodium bicarbonate in an experimental model of radiocontrast nephropathy

Aim: The aim of this study is to investigate the efficacy and mechanism of action of intravenous (IV) bicarbonate in preventing radiocontrast nephropathy (RCN). Materials and methods: Twenty-eight Wistar rats were randomized into four groups including control (group 1), radiocontrast (group 2), bicarbonate (group 3), and radiocontrast plus bicarbonate (group 4). Once blood chemistry and arterial blood gases were examined and 24 h urine samples were collected, all rats were administered furosemide (2 mg/kg subcutaneous) and deprived of water for 24 h. Iothalamate sodium (6 mL/kg) was administered to group 2 and group 4. IV bicarbonate (8.4%) was administered to group 3 and group 4 (3 h before the administration of iothalamate). On the fourth day, 24 h urine was collected, and at the end of the day rats were sacrificed and blood chemistry and arterial blood gases were reexamined. Myeloperoxidase (MPO), nitric oxide (NO), total glutathione, and malondialdehyde were quantified on the renal tissue. H&E slides were examined. Results: Basal creatinine and creatinine clearance were similar between groups. There was no significant difference between creatinine and creatinine clearance by the end of the experiment. Glutathione level in group 2 was lower than in group 4. Histopathologically, there was no injury in the control group (group 1) whereas there was an intermediate-severe injury (71.4%) in the radiocontrast group (group 2). The percentage of intermediate-severe injury was significantly lower (71.4% vs. 28.6%, p = 0.02) in the radiocontrast plus bicarbonate group (group 4). Conclusions: Sodium bicarbonate attenuates the development of radiocontrast-induced tubular necrosis.

Heme oxygenase-1 protects against radiocontrast-induced acute kidney injury by regulating anti-apoptotic proteins

Radiocontrast agents are thought to induce acute kidney injury in part through increased production of reactive oxygen species and increased cellular apoptosis. In this study we determined whether heme oxygenase-1 could prevent or reduce radiocontrast-induced acute kidney injury and, if so, what were the mechanisms by which this can occur. Sodium iothalamate was administered to uninephrectomized, salt-depleted male Sabra rats to initiate acute kidney injury. Heme oxygenase-1 was induced with cobalt protoporphyrin or inhibited with stannous mesoporphyrin. Inhibition of heme oxygenase exacerbated kidney injury as measured by an increase in plasma creatinine and in superoxide production. Heme oxygenase-1 induction prevented the increase in plasma creatinine and in superoxide in both the cortex and medulla compared to untreated rats with acute kidney injury. This protective effect of heme oxygenase-1 was associated with increased anti-apoptotic proteins Bcl-2 and Bcl-xl and a decrease of pro-apoptotic caspase-3 and caspase-9 along with increased expression of inactive BAX. Our study suggests that increased levels of heme oxygenase-1 are protective against acute kidney injury due to radiocontrast exposure.

Influence of Morbid Obesity on the Single-Dose Pharmacokinetics of Daptomycin

The present study characterized the single-dose pharmacokinetics of daptomycin dosed as 4 mg/kg of total body weight (TBW) in seven morbidly obese and seven age-, sex-, race-, and serum creatinine-matched healthy subjects. The glomerular filtration rate (GFR) was measured for both groups following a single bolus injection of [(125)I]sodium iothalamate. Noncompartmental analysis was used to determine the pharmacokinetic parameters, and these values were normalized against TBW, ideal body weight (IBW), and fat-free weight (FFW) for comparison of the two groups. All subjects enrolled in this study were female, and the mean (+/-standard deviation) body mass index was 46.2 +/- 5.5 kg/m(2) or 21.8 +/- 1.9 kg/m(2) for the morbidly obese or normal-weight group, respectively. The maximum plasma concentration and area under the concentration-time curve from dosing to 24 h were approximately 60% higher (P < 0.05) in the morbidly obese group than in the normal-weight group, and these were a function of the higher total dose received in the morbidly obese group. No differences in daptomycin volume of distribution (V), total clearance, renal clearance, or protein binding were noted between the two groups. Of TBW, FFW, or IBW, TBW provided the best correlation to V. In contrast, TBW overestimated GFR through creatinine clearance calculations using the Cockcroft-Gault equation. Use of IBW in the Cockcroft-Gault equation or use of the four-variable modification of diet in renal disease equation best estimated GFR in morbidly obese subjects. Further studies of daptomycin pharmacokinetics in morbidly obese patients with acute bacterial infections and impaired renal function are necessary to better predict appropriate dosage intervals.

Glibenclamide Effects on Renal Function and Histology after Acute Hemorrhage in Rats under Sevoflurane Anesthesia

Introduction. Hypovolemia from hemorrhage evokes protective compensatory reactions, such as the renin-angiotensin system, which interferes in the clearance function and can lead to ischemia. This study was designed to evaluate the effects of glibenclamide, a K+ATP channel blocker, on renal function and histology in rats in a state of hemorrhagic shock under sevoflurane anesthesia. Material and Methods. Twenty Wistar rats were randomized into two groups of 10 animals each (G1 and G2), only one of which (G2) received intravenous glibenclamide (1 μg.g−1), 60 min before bleeding was begun. Both groups were anesthetized with sevoflurane and kept on spontaneous respiration with oxygen-air, while being bled of 30% of volemia in three stages with 10 min intervals. There was an evaluation of renal function—sodium para-aminohippurate and iothalamate clearances, filtration fraction, renal blood flow, renal vascular resistance—and renal histology. Renal function attributes were evaluated at three moments: M1 and M2, coinciding with the first and third stages of bleeding; and M3, 30 min after M2, when the animals were subjected to bilateral nephrectomy before being sacrificed. Results. Significant differences were found in para-aminohippurate clearance, G1 < G2, and higher renal vascular resistance values were observed in G1. Histological examination showed the greater vulnerability of kidneys exposed to sevoflurane alone (G1) with higher scores of vascular and tubular dilatation. There were vascular congestion and tubular vacuolization only in G1. Necrosis and signs of tubular regeneration did not differ in both groups. Conclusion. Treatment with glibenclamide attenuated acutely the renal histological changes after hemorrhage in rats under sevoflurane anesthesia.

Rat Model of Depending Prostaglandin Renal State: Effect of Ketoprofen

Introduction.The renal prostaglandins (PGs), vasodilators, preserve kidney function during increased activity of the renin-angiotensin system or renal sympathetic nerves (renal PG-dependent state [RPGD]). Ketoprofen (Ket) inhibits cyclooxygenase and, therefore, the synthesis of PGs. The aim of this study was to determine, in the rat, the action of Ket in the renal histology and function in a RPGD state (stress of anesthesia and hemorrhage). Material and Methods. Twenty male Wistar rats, anesthetized with sodium pentobarbital, were randomly divided into two groups: G1—control (n = 10) and G2—Ket (n = 10) submitted to arterial hemorrhage of 30% of volemia (estimated as 6% of body weight) three times (10% each 10 min), 65 min after anesthesia. G2 animals received Ket, 1.5 mg. kg-1, venously, 5 min after anesthesia and 60 min before the first hemorrhage moment (first moment of the study [M1]). Medium arterial pressure (MAP), rectal temperature (T), and heart rate were monitored. G1 and G2 received para-aminohippurate sodium (PAH) and iothalamate sodium (IOT) solutions during the entire experimental time in order to determine clearance of PAH (effective renal plasma flow [ERPF]) and clearance of IOT (glomerular filtration rate [GFR]) without urine collection (determination of blood concentrations of PAH and IOT through the high-performance liquid chromatography), filtration fraction (FF), and renal vascular resistance (RVR). The animals were sacrificed in M3, 30 min after the third hemorrhage (M2) moment, and the kidneys and blood collected during the hemorrhage periods were utilized for histological study and determinations of hematocrit (Ht), serum creatinine (SCr), ERPF, GFR, FF, and RVR, respectively. Results. There were significant reductions of MAP, T, and Ht and a significant increase of SCr. During the experiment, ERPF and GFR did not change, but ERPF was always higher in G1 than in G2. Ket did not alter FF, which increased in G1 over the duration of experiment. The Ket group had significantly higher RVR than the control group. The histology verified that both G1 and G2 were similar for tubular dilation and necrosis, but they were significantly different for tubular degeneration: G1 > G2. Conclusion. The changes observed in kidney histology probably were determined by hemorrhage and hypotension. Ket inhibited the synthesis of PGs and diminished tubular degeneration.

Helical computed tomographic portography in ten normal dogs and ten dogs with a portosystemic shunt.

Contrast enhanced helical computed tomography (CT) of the liver and portal system is routinely performed in human patients. The purpose of this project is to develop a practical protocol for helical CT portography in the dog. Ten clinically normal dogs were initially evaluated to develop a protocol. Using this protocol, ten dogs with confirmed portosystemic shunts (PSS) were then evaluated. Each patient was anesthetized, and a test dose of sodium iothalamate (400 mg I/ml) at 0.55 ml/kg was injected. Serial images were acquired at the level of T12-13 or T13-L1. The time to maximum enhancement of the portal vein was determined. This time period was used as the period between the second injection (2.2 ml/kg) and the start of the helical examination of the cranial abdomen. Delay times for normal dogs ranged from 34.5 s-66.0 s (median: 43.5 s) or 1.41 s/kg-4.12 s/kg (median: 2.09 s/kg). For patients with a PSS, the delay times were 16.5-70.5 s (median: 34.5 s) or 1.47-19.17 s/kg (median: 3.39 s/kg). The aorta, caudal vena cava, portal vein, shunt vessels, and their respective branches were well visualized on the CT images. Clinical case results were surgically confirmed. The surgeons reported that the information gained from the CT portography resulted in a subjective decrease in surgical time and degree of dissection necessary compared with similar surgeries performed without angiographic information. We believe that helical CT portography in the dog will be a useful adjunct in the diagnosis of PSS. The use of helical CT portography may allow clinicians to give clients a more accurate prognosis prior to surgery and will allow patients with lesions that are not surgically correctable to avoid a costly and invasive procedure.

Diuretic Doppler ultrasonography in chronic unilateral partial ureteric obstruction in dogs.

To compare the effects of diuresis induced by a loop diuretic (frusemide), an osmotic diuretic (mannitol) and a high-osmolar radio-contrast medium (sodium iothalamate) on the intrarenal resistive index (RI) in dogs with chronic unilateral partial ureteric obstruction (UPUO). The split renal clearance and intrarenal RI were estimated in 11 dogs with chronic UPUO. Doppler ultrasonography measurements of the interlobar arteries were obtained before and 10 min after the intravenous infusion of 1 mg/kg frusemide, 1 g/kg mannitol or 20 mL 60% sodium iothalamate. The same experimental protocol was repeated with another drug at 1-week intervals. There was a significant difference between the intrarenal RI of obstructed and unobstructed kidneys in the chronic phase of UPUO. While mannitol and sodium iothalamate significantly increased the RI in both kidneys, differences in RI between the kidneys decreased after infusing the two drugs. However, while frusemide insignificantly increased the RI in the obstructed kidney, it decreased the RI in unobstructed one. Consequently, the difference in RI between the kidneys increased significantly after administering frusemide. There were no significant differences in urinary volume after administering each of the drugs. As there were no significant differences in the diuretic effects of the drugs, frusemide may have additional effects on the RI of unobstructed kidneys other than diuresis. Frusemide increased the difference between the intrarenal RI of the kidneys and therefore may improve the detection of unilateral urinary obstruction in humans.

Effects of tezosentan, a dual endothelin receptor antagonist, on the cardiovascular and renal systems of neonatal piglets

Background/Purpose: Endothelin is a potent biological vasoactive mediator in the cardiovascular and renal systems. Little is known of the effects of endothelin antagonism on the developing heart and kidney, and we hope to show that endothelin does have an important role in the cardiovascular and renal systems of the developing neonate. In this study the authors have examined the effects of tezosentan, a nonselective endothelin-A and endothelin-B receptor antagonist designed for parenteral use, on the cardiovascular and renal systems of healthy neonatal piglets. Methods: Eight, 7- to 10-day old domestic piglets weighing 2.5 to 3.0 kg were anesthetized, intubated, and ventilated with catheters placed into the jugular vein, left ventricle, and femoral artery. Urine output was monitored via a suprapubic cystostomy. After baseline data were obtained the piglets received tezosentan (1 mg/kg/h) for 1 hour. A set of data was collected just before discontinuation of the 1-hour infusion of tezosentan and another set was collected 1 hour after the discontinuation of the drug. Mean arterial pressure (MAP), heart rate (HR), and urine output (UV) were monitored continuously and cardiac index (CI), systemic vascular resistance (SVR), renal blood flow (RBF), and renal vascular resistance (RVR) were calculated from gamma counts obtained from injections of radio-labeled microspheres at end of the different time periods. Glomerular filtration rate (GFR) was obtained by the sodium iothalamate method. Data were averaged and plotted versus time and analyzed statistically by a Student's t test. Results: (P < .05 versus baseline*). In our experimental animals the infusion of tezosentan diminished MAP and SVR from baseline values of 94 ± 7 mm Hg and 0.14 ± 0.03 mm Hg/mL/min, respectively to TEZO values of 62 ± 4* mm Hg and 0.07 ± 0.02* mm Hg/mL/min. CI increased from 278 ± 58 to 367 ± 75* mL/min/kg with tezosentan. There also was a statistically significant increase in RBF from 1.16 ± 0.38 to 1.86 ± 0.37* mL/min/kg, an increase in UV from 0.57 ± 0.24 to 0.64 ± 0.12* mL/min, a decrease in RVR from 4.60 ± 1.47 to 2.03 ± 0.36* mm Hg/mL/min, and no change in the GFR. Conclusions: The inhibition of endothelin receptors with tezosentan produced a statistically significant effect on the piglet cardiovascular system with a drop in MAP and SVR and an increase in CI and HR. It also produced a statistically significant increase in RBF and UV and a decrease in RVR without affecting GFR. J Pediatr Surg 36:1824-1828. Copyright © 2001 by W.B. Saunders Company.

Changes in intrarenal oxygenation as evaluated by BOLD MRI in a rat kidney model for radiocontrast nephropathy.

The pathogenesis of radiocontrast nephropathy is poorly understood. In an animal model, inhibition of the synthesis of nitric oxide and prostaglandins appears to predispose rats to severe renal injury following the administration of radiocontrast. Here we have investigated whether administration of radiocontrast, as well as changes in renal medullary oxygenation following pharmacologic inhibition of nitric oxide and prostaglandin synthesis, might be evaluated by blood oxygenation level-dependent (BOLD) MRI. Nineteen anesthetized (Inactin 100 mg/kg) rats were studied. BOLD MRI measurements were performed following administration of L-NAME (N-nitro-L-arginine methyl ester, 10 mg/kg), Indomethacin (10 mg/kg), and a radiocontrast agent (sodium iothalamate 60%, 6 mL/kg). Marked sequential changes in medullary R(*)(2), presumably reflecting decline in medullary pO(2), were noted after each of the pharmacological interventions employed. These results, obtained by noninvasive MRI, are consistent with prior direct recordings of pO(2) and doppler flow in the rat renal medulla after administration of L-NAME, Indomethacin and iothalamate. Medullary oxygenation in rats was reduced by inhibition of the synthesis of prostaglandins and nitric oxide, as well as by intravenous injection of radiocontrast agents. BOLD MRI can noninvasively evaluate changes in medullary oxygenation in rats that appear to predispose acute renal failure. J. Magn. Reson. Imaging 2001;13:744-747.

Creation of Radiopaque Thrombi for In Vivo Experiments

A number of percutaneous thrombectomy devices are undergoing investigation for treatment of patients with venous thromboembolism. Use of radiopaque thrombus to monitor thrombus delivery and assess thrombectomy has been previously reported. The purpose of this project was to quantitatively test the effect of mixing different ratios of blood and contrast material to facilitate maximum thrombus formation and radiopacity. The following ratios of blood and contrast material were mixed: 2 mL blood to 8 mL contrast material (ratio = 0.25), 4 mL blood to 6 mL contrast material (ratio = 0.67), 6 mL blood to 4 mL contrast material (ratio = 1.5), and 8 mL blood to 2 mL contrast material (ratio = 4). Contrast material was added at day 0, 3, or 6. Each sample received one of two ionic contrast agents to opacify the clots. At day 14, thrombus mass and opacity were determined. Three combinations of blood and contrast material produced maximum thrombus and radiopacity. These were sodium iothalamate 30% with a ratio of 4 with contrast material added on day 0 and sodium iothalamate 60% with a ratio of 1.5 with contrast material added on day 3 or 6. When forming radiopaque thrombi, significant differences can result from the ratio of blood to contrast material used. Contrast material type can also affect radiopacity and mass formed. The use of optimal ratios of blood to contrast material should maximize device evaluation with minimal wasting of valuable resources such as test subjects, physician time, and equipment.

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients.

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5-8 years. Post-transplant sodium iothalamate clearances (IoCI) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20 % reduction in IoCl over 2 consecutive years) in IoCl. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after anti-rejection therapy. The incidence of AR was not significantly different between groups (47% vs 52%). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100% (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (8/25) of the patients in the decline group had complete reversal (P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 % (14/17) lost their grafts to CR. Overall, only 8% (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed.

Adverse reactions to radiocontrast media in an Indian population.

This study was conducted to determine the epidemiological characteristics and clinical presentation of adverse reactions to intravenous radiocontrast media (CM) in patients of Indian origin. 379 of 1798 patients who received either sodium iothalamate or sodium meglumine diatrizoate developed adverse reactions (i.e. 21.08% of patients). The incidence of mild, moderate and severe adverse reactions were 19.47%, 1.33% and 0.28%, respectively. One patient who developed a severe reaction expired. There were no differences in the incidence of adverse reactions according to gender (males 21.2%; females 20.8%; p = 0.907) or age (p = 0.876). The incidence of adverse reactions was significantly higher in patients with a history of previous reactions (45.5%) than in those with no history (20.9%; p = 0.046). The incidence of reactions was also significantly higher in patients with a history of predisposing factors such as bronchial asthma (69.2%) and diabetes mellitus (60.0%) than in those without such a history (20.6%; p = 0). The incidence of adverse reactions in patients who received premedication prior to CM administration because of a history of predisposing factors (21.4%) was not significantly different from that in patients who were not premedicated (21.2%; p = 0.974), a result probably due to inadequate premedication used in the study. The skin was the most commonly affected site of reaction.

Effect of Radiocontrast Agents on Intrarenal Nitric Oxide (NO) and NO Synthase Activity

Background/Aims: Contrast media (CM) induce a biphasic renal hemodynamic response, with late prominent cortical vasoconstriction and marked outer medullary vasodilation. The objective of the study was to explore a possible role for altered nitric oxide (NO) production or bioavailability in these hemodynamic responses. Methods: We explored the impact of CM (sodium iothalamate) upon rat renal NO synthase (NOS) activity (citrulline recovery) and NO (using a NO electrode). Results: The cortical NOS activity following CM was 11.5 ± 1.0 versus 13.8 ± 1.1 nmol/gww/min (gww = gram wet weight) in controls (p = 0.16, NS). In rats pretreated with the nonselective endothelin antagonist bosentan, CM reduced the cortical NOS activity to 8.5 ± 1.2 nmol/gww/min (p < 0.005 vs. controls). Cortial NO readings declined over 30 min following CM by 13 ± 8% (p < 0.05, Anova), in parallel with the decline in cortical blood flow. The outer medullary NOS activity was not affected by CM (5.2 ± 1.5 vs. 5.5 ± 1.3) nmol/gww/min in controls) or bosentan. Nevertheless, the outer medullary NO reading increased by 36 ± 23% (p < 0.05), with a concomitant increase in regional blood flow. Conclusion: In the cortex, CM might reduce the NOS activity (an effect blunted by endothelin release). This may potentiate the effect of endothelin to induce regional vasoconstriction. In the outer medulla, the vasodilatory response to CM does not seem to be mediated by enhanced NOS activity and might reflect increased local NO bioavailability as the result of regional hypoxia.

Do Iodinated Contrast Agents Affect Prognosis in Acute Experimental Cerebral Ischemia?

We studied the effects of ionic and non-ionic iodinated contrast agents in acute cerebral ischemia on infarction volume, neurological performance, and mortality in a rat model of middle cerebral artery (MCA) occlusion. We induced focal cerebral ischemia in 64 rats using an endovascular occlusion technique of the MCA. Four hours after MCA occlusion, 16 animals received sodium iothalamate (588 mg iodine/kg), 16 animals received iopromide as single bolus (518 mg iodine/kg) and 16 animals as double bolus (1036 mg iodine/kg). Sixteen animals received equivolumetric (1.4 ml/kg) saline (control group). Neurological score and body weight were recorded every 8 hours. Twenty-four hours after vessel occlusion all animals were sacrificed and their brains stained with 2,3,5 triphenyl-tetrazolium-chloride (TTC) to assess infarction size. The normal and the double clinical dose of iopromide did not affect infarction volume and neurological performance. Sodium iothalamate caused an increase in infarction volume and worse...

Faster and easier radiochemical purity testing for [125I]sodium iothalamate.

A previous method for determination of the radiochemical purity (RCP) value of [125I]sodium iothalamate uses two paper strips and solvents (total developing time is approximately 2.5 h). To simplify and shorten the RCP testing procedure, our laboratory has developed a single-strip chromatography method that not only distributes free 125I and [125I]sodium iothalamate to different relative front (Rf) locations, but is also faster and easier to perform. RCP of [125I]sodium iothalamate was determined with the use of a 10-cm instant thin-layer chromatography strip impregnated with polysilicic acid gel (ITLC-SA) as the solid phase, and a mobile phase of 2-butanol:acetic acid:water (140:2.5:70, v/v). By using autoradiography and counting the strip segments in a gamma counter, our results indicated that free 125I migrated to Rf = 0.89-1.00 while the [125I]sodium iothalamate moved to Rf = 0.44-0.67. The total developing time for the single-strip ITLC-SA system was approximately 1 h.

Faster and easier radiochemical purity testing for [ 125I]sodium iothalamate

A previous method for determination of the radiochemical purity (RCP) value of [ 125I]sodium iothalamate uses two paper strips and solvents (total developing time is ∼2.5 h). To simplify and shorten the RCP testing procedure, our laboratory has developed a single-strip chromatography method that not only distributes free 125I and [ 125I]sodium iothalamate to different relative front (R f) locations, but is also faster and easier to perform. RCP of [ 125I]sodium iothalamate was determined with the use of a 10-cm instant thin-layer chromatography strip impregnated with polysilicic acid gel (ITLC-SA) as the solid phase, and a mobile phase of 2-butanol:acetic acid:water (140:2.5:70, v/v). By using autoradiography and counting the strip segments in a gamma counter, our results indicated that free 125I migrated to R f = 0.89–1.00 while the [ 125I]sodium iothalamate moved to R f = 0.44–0.67. The total developing time for the single-strip ITLC-SA system was ∼ 1 h.

Bronchial vasodilatory response to ionic and nonionic contrast media.

It has recently been shown that bronchial arterial injection of conventional contrast medium causes a significant increase in bronchial blood flow (Qbr) and that this response is partially attenuated after infusion of N omega-nitro-L-arginine (L-NNA). However, the precise mechanism for this increase in Qbr is unknown. In this study we examined the effect of bronchial arterial injection of conventional ionic as well as nonionic contrast media. We measured Qbr in nine anesthetized, ventilated, open-chest sheep. Qbr was recorded before (baseline) and at the peak response to injection of 0.5 ml of either 0.9% saline (control; isosmolar with plasma), Omnipaque 300 (iohexol; nonionic), Conray 66 (sodium iothalamate; ionic), or 50% dextrose (viscous control). Measurements were made during a control period, after infusion of the alpha-agonist phenylephrine (5 x 10(-6) to 5 x 10(-7) M), and after bronchial arterial infusion of L-NNA (10(-2) M). The results were as follows: bronchial arterial injection of saline, Omnipaque, Conray, and dextrose caused an increase in Qbr (P < 0.05). During the control period, increases in peak Qbr on injection of saline, Omnipaque, Conray, and dextrose were 55 +/- 29, 112 +/- 62, 280 +/- 99, and 388 +/- 125% of baseline, respectively. Bronchial arterial infusion of L-NNA lowered baseline Qbr and partially attenuated the response to injection of saline, Omnipaque, and Conray (P < 0.05). Phenylephrine, in doses that decreased baseline Qbr to the same extent as did L-NNA, did not attenuate the bronchial vasodilation. There was a linear relationship between osmolality and the percentage increase in bronchial blood flow. We conclude that an osmolar stress is the trigger for the contrast-induced bronchial vasodilation and that the response is partially mediated by endothelial release of nitric oxide.

Urineless estimation of glomerular filtration rate and renal plasma flow in the rat

A simple method to perform serial renal clearance studies without urine collection in rats is described. This was applied to nonradiolabelled para-aminohippurate sodium (PAH) and iothalamate sodium (IOT) which were used respectively to estimate renal plasma flow (RPF) and glomerular filtration rate (GFR). Under isoflurane-anesthesia the jugular vein and carotid artery of Fischer 344 rats were cannulated, and a loading dose followed by a continuous infusion of PAH and IOT was administered. Steady state was reached after 30 min, and four arterial blood samples were collected over the next 30 min for analysis by HPLC (day 0). The clearances of PAH and IOT were calculated according to Fick's principle as estimates of RPF and GFR from the ratio of the infusion rates to the median solute concentrations. Three days later the femoral artery and vein were cannulated, and the same study was repeated (day 3). There was no significant difference in renal clearances of PAH and IOT between days 0 and 3. The described method gives values that compare well with others in the literature based on other methods and presents an accurate and simple way of detecting changes in renal function before and after a potentially nephrotoxic treatment regimen.

A role for nitric oxide in x-ray contrast material toxicity

We assessed the role that nitric oxide (NO) plays in contrast media (CM) toxicity, using 100% lethal dose (LD100) studies in hyperimmune Brown Norway (BN) rats. Ninety-two BN rats and 41 Sprague-Dawley (SD) rats underwent CM LD100 tail vein injections with methylglucamine iothalamate or sodium iothalamate to the point of cessation of respiration. Methylglucamine hydrochloride also was injected. The injections were accompanied by L-arginine (L-Arg) or D-arginine (D-Arg) analogues or by an H1 blocker. L-Arg analogues inhibit NO formation, and D-Arg analogues do not. An L-Arg analogue, but not a D-Arg analogue, increased the tolerance of BN rats (p < .005) for methylglucamine iothalamate but not for sodium iothalamate. The L-Arg analogue also protected BN rats against methylglucamine chloride injections (p < .002). H1 blockade protected BN rats against methylglucamine iothalamate (p < .0005) and methylglucamine chloride (p < .005) injections. None of these measures altered the CM tolerance of SD rats. In SD rats, injections of either methylglucamine iothalamate or sodium iothalamate along with a D-Arg analogue or normal saline were better tolerated than similar injections in BN rats (p < .01 and .002 for methylglucamine iothalamate and sodium iothalamate, respectively). In SD rats but not BN rats, sodium iothalamate was better tolerated than was methylglucamine iothalamate (p < .0005). NO appears to play a significant role in BN rats LD100 CM toxicity and has been implicated by others in the blood pressure fall characterizing some forms of antigen-induced anaphylaxis [1, 2]. The results of the current study and the literature suggest that methylglucamine-modulated release of histamine from mast cells may underlie the NO production.

Modified radioiodination and quality control methods for [ 125I]sodiuin iothalamate

[ 125I]Sodium iothalamate can be prepared by the isotope-exchange method with the use of a contrast medium preparation (i.e. iothalamate sodium injection, USP, 80%). The initial isolation and purification of iothalamate from the contrast medium solution for radioiodination is tedious and time-consuming (i.e. 1 1 2 h for purification and overnight for drying). The new method uses iothalamic acid to replace iothalamate sodium injection as a starting material and reduces the heating time and multiple acid-washing steps during radioiodination to expedite the radiolabelling process. The radiochemical purity (RCP) of [ 125I]sodium iothalamate obtained from the new method was 98.9±1.3% ( n = 30) versus RCP value of 99.2 ± 1.0% ( n = 25) from the old method with no significant differences between the two groups of RCP values. An RCP chromatographical system to separate and migrate the radiochemical species of [ 125I]sodium iothalamate from the origin is described in this paper.