Comparative cytotoxicity of ionic and non-ionic radiocontrast agents on MDCK cell monolayers in vitro.
BACKGROUND: Intravascular radiocontrast agents may cause acute renal failure, particularly in patients with pre-existing renal insufficiency. Direct cytotoxic effects of radiocontrast agents on renal tubular cells may contribute to the pathogenesis of radiocontrast-induced nephropathy. METHODS: We analysed the cytotoxicity of the ionic radiocontrast agents diatrizoate (monomeric) and ioxaglate (dimeric), as well as of the non-ionic radiocontrast agents iohexol (monomeric) and iodixanol (dimeric) on the renal epithelial Madin Darby Canine Kidney (MDCK) cell line grown on permeable supports. The toxicity assays assessed cell viability, transmonolayer resistance and inulin permeability between the apical and basal cell culture compartment. In addition, the distribution of the tight-junction-associated membrane proteins ZO-1 and occludin was analysed using immunofluorescence microscopy. RESULTS: In all assays the high osmolal ionic compound diatrizoate had significant cytotoxic effects that included the partial redistribution of the tight-junction-associated membrane proteins into a cytoplasmic compartment. To a lesser extent this redistribution also occurred with the dimeric ionic compound ioxaglate, but not with the non-ionic radiocontrast agents. With regards to cell viability, transmonolayer resistance and inulin permeability the radiocontrast agents with reduced osmolality were significantly less toxic than diatrizoate, independent of their ionic strength. CONCLUSIONS: Physicochemical factors contribute to the cytotoxicity of radiocontrast agents in vitro. The redistribution of tight-junction-associated membrane proteins by the ionic radiocontrast agents corresponds with the loss of the barrier function of the epithelial cell monolayer, which is a major pathophysiological mechanism in acute renal failure. The radiocontrast agents with reduced osmolality are less cytotoxic than diatrizoate, independent of their ionicity. Hyperosmolality appears to be a more important determinant of the cytotoxicity of diatrizoate than ionic strength. (+info)
Should initial clamping for abdominal aortic aneurysm repair be proximal or distal to minimise embolisation?
OBJECTIVES: to determine whether clamping proximally or distally on the infrarenal aorta during abdominal aortic aneurysm (AAA) repair increases the overall embolic potential. MATERIALS AND METHODS: a sheath was placed in the mid-infrarenal aorta of 16 dogs. In eight animals a cross-clamp was placed at the aortic trifurcation, and in another eight animals it was placed in the immediate subrenal position. Under fluoroscopy blood flow within the infrarenal aorta was evaluated by contrast and particle injections. Grey-scale analysis was used to calculate contrast density. Particle distribution was followed fluoroscopically and confirmed pathologically. RESULTS: fifty-seven+/-24% of injected contrast remained within the aorta with distal clamping while 97+/-7% did so with proximal clamping (p<0.01). With distal aortic clamping 6.2+/-1. 3 out of 10 injected particles remained within the aorta after 15 seconds and only 0.8+/-0.8 remained after 5 min. With proximal aortic clamping, all 10 of the particles remained within the aortic lumen for the full 5 minutes (p<0.001). CONCLUSIONS: initial distal clamping minimises distal embolisation, but may result in renal and/or visceral embolisation. Initial proximal clamping prevents proximal embolisation and does not promote distal embolisation. We recommend initial proximal clamping in aortic aneurysm surgery to minimise the overall risk of embolisation. (+info)
Validation of minimally invasive measurement of myocardial perfusion using electron beam computed tomography and application in human volunteers.
OBJECTIVES: To measure myocardial perfusion using an estimate of intramyocardial vascular volume obtained by electron beam computed tomography (EBCT) in an animal model; to assess the feasibility and validity of measuring regional myocardial perfusion in human volunteers using the techniques developed and validated in the animal studies. METHODS: Measurements of myocardial perfusion with EBCT employing intravenous contrast injections were compared with radioactive microsphere measurements (flow 57 to 346 ml/100 g/min) in seven closed chest dogs. Fourteen human volunteers then underwent EBCT scans using intravenous contrast injections. RESULTS: Mean (SEM) global intramyocardial vascular volume by EBCT was 7.6 (1.1)%. The correlation between global EBCT (y) and microsphere (x) perfusion was y = 0.59x + 15.56 (r = 0.86) before, and y = 0.72x + 6. 06 (r = 0.88) after correcting for intramyocardial vascular volume. Regional perfusion correlation was y = 0.75x + 23.84 (r = 0.82). Corresponding improvements in agreement between the two techniques were also seen using Bland-Altman plots. In the human subjects, mean resting global myocardial flow was 98 (6) ml/100 g/min, with homogeneous flow across all regions. In 10 of these subjects, perfusion was studied during coronary vasodilatation using intravenous adenosine. Global flow increased from 93 (5) ml/100 g/min at rest to 250 (19) ml/100 g/min during adenosine (p < 0.001), with an average perfusion reserve ratio of 2.8 (0.2). Similar changes in regional perfusion were observed and were uniform throughout all regions, with a mean regional perfusion reserve ratio of 2.8 (0.3). CONCLUSIONS: Accounting for intramyocardial vascular volume improves the accuracy of EBCT measurements of myocardial perfusion when using intravenous contrast injections. The feasibility of providing accurate measurements of global and regional myocardial perfusion and perfusion reserve in people using this minimally invasive technique has also been demonstrated. (+info)
Iodinated radiographic contrast media inhibit shear stress- and agonist-evoked release of NO by the endothelium.
1 We have used isolated arterial preparations from the rabbit and dog to investigate whether non-ionic iodinated radiographic contrast media (IRCM) modulate nitric oxide (NO) release. The tri-iodinated monomers iopromide and iohexol were compared with the hexa-iodinated dimer iodixanol. 2 The vasodilator effects of iohexol (300 mg ml-1) and iodixanol (320 mg ml-1) were assessed in cascade bioassay. Increasing concentrations of iohexol or iodixanol caused concentration-dependent relaxations of the detector tissue which were insensitive to 100 microM NG-nitro L-arginine methyl ester (L-NAME) and 10 microM indomethacin, whereas viscosity-associated relaxations induced by the 'inert' agent dextran (MW 80,000; 1-4%) were attenuated by inhibition of NO synthesis. 3 Relaxations of endothelium-intact rings to acetylcholine (ACh) were attenuated by preincubation with iohexol or iodixanol, whereas relaxations to sodium nitroprusside (SNP) in endothelium-denuded rings were unaffected. Inhibitory activity did not correlate with either molarity or iodine concentration. Mannitol caused inhibition of both ACh- and SNP-induced responses. 4 In isolated perfused arteries the depressor responses to iodixanol (320 mg ml-1) and iopromide (300 mg ml-1) administered as close arterial bolus attained a plateau with maximal dilatations of approximately 25% and approximately 60%, respectively. Addition of 100 microM NG-nitro L-arginine (L-NOARG) and/or 10 microM indomethacin to the perfusate had no effect on the responses to either agent. 5 We conclude that IRCM exert direct effects on the endothelium that inhibit NO production rather than its action on vascular smooth muscle. Shear stress-induced stimulation of NO production by IRCM is unlikely to contribute to their vasodilator activity in vivo when administered during angiography despite high intrinsic viscosity. (+info)
Improved clearance of iohexol with longer haemodialysis despite similar Kt/V for urea.
BACKGROUND: The efforts to improve the quality of haemodialysis (HD) has renewed the interest in the consequences of blood-flow distribution for removal of solutes. METHODS: To test the effects of HD time per se, 10 patients were studied in a cross-over fashion with HD for 3 h and 1 week later for 6 h, with similar blood urea Kt/Vs, achieved by adjusting the blood flow rate to 290 and 120 ml/min respectively. Injections of iohexol (MW 821 Dalton) were given 2 days prior to the dialysis sessions. Blood samples were taken before, during (6/HD), 1 and 24 h after the HD and analysed for concentrations of urea and iohexol. A urea on-line monitor (Gambro) was used for continuous recordings and sampling of dialysate. RESULTS: According to the study design the blood Kt/V for urea (Daugirdas II) was similar for 3 and 6 h HD, close to 1.0 (n.s), while the removed mass of urea showed that Kt/V was slightly and significantly higher for the 6 h HD. The 'apparent' mass of iohexol, defined as plasma concentration times estimated distribution volume, fell to 29% and 21% of pre-dialysis levels after 3 h and 6 h HD, respectively (P<0.01), but increased after HD, and more so after the short dialysis, reaching 46% of the predialysis mass 24 h after 3 h HD vs. 36% after 6 h HD (P<0.05). The removed mass of iohexol was 920+/-110 mg with 6h HD and 700+/-81 mg with 3h HD, (P<0.01). Thus, the longer dialysis removed 32% more iohexol despite similar blood Kt/V for urea. CONCLUSION: The treatment time per se affects solute removal despite similar blood Kt/V for urea. This is particularly true for an intermediate-size molecule like iohexol. (+info)
Contrast-enhanced spiral CT of the head and neck: comparison of contrast material injection rates.
BACKGROUND AND PURPOSE: Contrast-enhanced spiral CT studies of the head and neck are performed frequently using contrast material volumes of approximately 30 g iodine and a scan delay of 30-45 seconds. Because little is known about the effects of contrast material injection rates on tissue enhancement, this was prospectively investigated in our study. METHODS: Ninety-seven patients underwent spiral CT of the head and neck. Each patient was assigned randomly to one of four groups who received 100 mL of nonionic contrast material (300 mg I/mL) at different monophasic injection flow rates with 1.5, 2, 3, and 4 mL/s. Scanning started after a constant delay of 35 seconds. The attenuation of the carotid artery, jugular vein, and sternocleidomastoid muscle was measured over time and the attenuation of the submandibular and thyroid gland was evaluated. Vascular attenuation of at least 150 HU was considered to be sufficient. RESULTS: The mean scan time was 33+/-5 seconds. The study, using an injection rate of 2 mL/s, showed the longest time of sufficient overall (arterial and venous) vessel attenuation (27+/-4 seconds, P< or =.008). The injection flow rate did not influence significantly muscular attenuation (mean enhancement during scan time: 9+/-7 HU). The 1.5 mL/s protocol showed the lowest attenuation values of the submandibular gland (81+/-12 HU) and the highest attenuation values of the thyroid gland (164+/-22 HU), but the attenuation of the thyroid gland was not statistically different from that revealed by the 2 mL/s protocol. CONCLUSION: Using 100 mL of intravenous contrast material with 300 mg I/mL for spiral CT studies of the entire head and neck, the optimal injection flow is 2 mL/s, whereas lower flow rates resulted in insufficient venous enhancement. (+info)
Elimination of non-ionic contrast medium by hemodialysis in patients with impaired renal function.
The elimination rate of iohexol, a non-ionic contrast medium, from the blood by hemodialysis, and the elimination rate of iohexol by a dialyzer were studied in 15 patients with chronic renal dysfunction who required angiography or enhanced CT. The elimination rate of iohexol was 19.8% at 15 min after the start of hemodialysis, 30.6% after 30 min, 44.2% after 1 hour, 62.1% after 2 hours and 72.9% after 3 hours. The dialyzer elimination rate was maintained at about 75% from 1 to 3 hours after the start of hemodialysis. If only about 70% of iohexol in the blood needs to be eliminated, hemodialysis for 3 hours with a blood flow rate of 120 ml/min and a dialysate flow of 500 ml/min using a 0.7 m2 cellulose triacetate membrane is sufficient. (+info)
The renal effect of low-dose dopamine in high-risk patients undergoing coronary angiography.
OBJECTIVES: The purpose of the study was to examine the potential renal protective effect of low-dose dopamine in high-risk patients undergoing coronary angiography. BACKGROUND: Contrast nephropathy is prevalent in patients with chronic renal failure (CRF) and/or diabetes mellitus (DM). Decreased renal blood flow due to vasoconstriction was suggested as a contributory mechanism. Low-dose dopamine has a dilatory effect on the renal vasculature. METHODS: Sixty-six patients with mild or moderate CRF and/or DM undergoing coronary angiography were prospectively double-blindedly randomized, to either 120 ml/day of 0.9% saline plus dopamine 2 microg/kg/min (Dopamine group) or saline alone (Control group) for 48 h. RESULTS: Thirty-three Dopamine-treated (30 diabetics and 6 with CRF) and 33 Control (28 diabetics and 5 with CRF) patients were compared. Plasma creatinine (Cr) level increased in the Control group from 100.6+/-5.2 before to 112.3+/-8.0 micromol/liter within five days after angiography (p = 0.003), and in the Dopamine group from 100.3+/-5.4 before to 117.5+/-8.8 micromol/liter after angiography (p = 0.0001), respectively. There was no significant difference in the change of Cr level (deltaCr) between the two groups. However, in a subgroup of patients with peripheral vascular disease (PVD), deltaCr was -2.4+/-2.3 in the Control group and 30.0+/-12.0 micromol/liter in the Dopamine group (p = 0.01). No significant difference occurred in deltaCr between Control and Dopamine in subgroups of patients with preangiographic CRF or DM. CONCLUSIONS: Contrast material caused a small but significant increase in Cr blood level in high-risk patients. There is no advantage of dopamine over adequate hydration in patients with mild to moderate renal failure or DM undergoing coronary angiography. Dopamine should be avoided in patients with PVD exposed to contrast medium. (+info)