Contrast media-induced blood-brain barrier damage. Potentiation by hypertension

Large doses of an ionic contrast medium (CM) can disrupt the blood brain barrier (BBB) osmotically. Acute hypertension (HT) also is known to open the BBB. We tested the hypothesis that these two factors potentiate each other in a rat model. Adult male Wistar rats, anesthetized with pentobarbital, underwent tracheostomy. An external carotid artery catheter was placed so that it opened into the patent common carotid artery; arterial blood pressure was recorded continuously. Of three groups of animals, two (HT) groups received metaraminol to elevate and maintain blood pressure in the range of 165 to 190 mm Hg. The third (normotensive) group received an equivalent volume of saline. Five minutes after injection of Evan's blue, either sodium/meglumine diatrizoate or saline was infused into the carotid cannula (2 mL in 30 seconds). Twenty minutes later the cardiovascular system was flushed with saline, and the brain was removed, frozen, and sectioned for gross and histofluorescent microscopic examination of BBB opening. The carotid injection of CM at a concentration of 1000 mosm/kg water did not produce gross evidence of BBB opening in the normotensive group. Similarly, hypertension at levels below 190 mm Hg did not produce gross evidence of opening in the carotid saline group. However, the combination of carotid CM and HT produced significant BBB opening. These results suggest that the risk factor of acute HT potentiates CM-induced BBB opening.     

Contrast media-induced compartment syndrome

Intravascular (IV) contrast media are essential in many cases to enhance the diagnostic capabilities of medical imaging procedures. Much is known about the indications, contraindications, and adverse events associated with their use. This Directed Reading focuses on extravasation and IV contrast media-induced compartment syndrome, a less frequent, although serious, adverse event. In addition to describing the compartments within the forearm, wrist, and hand, the article explains how compartment syndrome develops, techniques used to treat the condition, and prevention strategies.     

Contrast media-induced renal morphologic changes in rats with acute edematous pancreatitis.

OBJECTIVES. Contrast media (CM)-induced renal morphologic changes were studied in rats during acute edematous pancreatitis. METHODS. The histologically verified, mild pancreatitis was caused in Wistar rats (n = 54) by an injection of peanut oil into the pancreatic duct. After 24 hours, the animals received an intravenous (IV) injection of 1.0 or 3.0 g iodine (I)/kg of high-osmolality diatrizoate, low-osmolality iopromide or iohexol, or 0.2 or 0.6 g/kg of high-osmolality magnetic resonance (MR) CM, gadolinium-DTPA (Gd-DTPA). The controls received physiologic saline. The kidneys were fixed by perfusion after 2 hours, and changes in renal morphology were analyzed semiquantitatively by two independent observers blinded to the treatment. RESULTS. The smaller dose of iohexol and the larger dose of all other CM induced a statistically significant (P less than .05) cytoplasmic vacuolization in the proximal convoluted tubule cells. The changes were most prominent after iohexol (P less than .001). When compared with the authors' earlier findings on healthy rats, the CM-induced renal structural injury was more severe. CONCLUSIONS. Pancreatitis potentiates the renal microstructural changes associated with CM; although the animals' fluid and electrolyte status was not specifically assessed, the enhanced abnormalities may be related to the hypovolemia associated with pancreatitis.     

Contrast media-induced effects on blood rheology and their importance in angiography.

Factors which alter blood viscosity may have important consequences during angiography. The differential effects of various concentrations of five different radiocontrast media on the viscosity characteristics of erythrocyte-plasma suspensions were made over a range of applied shear rates. The results showed that, at both high and low shear rates, the rate of change of viscosity with contrast concentration differs markedly between the various types of contrast media. The conventional ionic monomers caused most disturbance to blood viscosity. The monoionic dimer hexabrix was least disturbing to the viscometric characteristics of blood, and the newer non-ionic monomers were intermediate in their effects. Significant effects on blood viscosity may be caused by radiocontrast agents during a number of in vivo angiographic situations, in particular: early after contrast bolus injection into large vessels, in the microcirculation after selective injections, and during angioplasty procedures.     

Contrast media-induced renal morphologic lesions during experimental hemorrhagic necrotizing pancreatitis.

RATIONALE AND OBJECTIVES. Contrast media-induced renal morphologic changes were studied in rats. Hemorrhagic pancreatitis was induced as a means of sensitizing the animals to the effects of contrast media. METHODS. The histologically verified hemorrhagic pancreatitis was induced in Wistar rats (n = 66) by injecting 6% sodium taurocholate into the pancreatic duct. After 2 hours, the animals received intravenously 1.0 or 3.0 g iodine/kg of high-osmolal osmolal diatrizoate, low-osmolal iopromide or iohexol, iso-osmolal iotrolan or 0.2 or 0.6 g/kg of high-osmolal magnetic resonance contrast agent, gadolinium-DTPA (Gd-DTPA). Control animals received physiologic saline. The kidneys were fixed by perfusion 2 hours later, and the morphologic changes were reviewed by two independent observers blinded to the injected agent. RESULTS. The smaller dose of iohexol and the larger dose of all the contrast media induced a statistically significant (P < .001 or .01) cytoplasmic vacuolization in the proximal convoluted tubule (PCT) cells. The nonionic, low- and iso-osmolal contrast media caused as much or even significantly more vacuolization than diatrizoate. CONCLUSIONS. Hemorrhagic pancreatitis potentiates the contrast media-induced renal morphologic changes, which depend on the type and dose of the injected contrast media.     

Contrast media-induced renal tubular vacuolization. A light and electron microscopic study on rat kidneys

The morphologic changes in healthy rat kidneys (n = 102) were studied 2 or 48 hours after intravenous injection of 1 or 3 g iodine (I)/kg of high-osmolality diatrizoate, low-osmolality iopromide and iohexol, or iso-osmolality iotrolan, as well as after 0.2 or 0.6 g/kg of the high-osmolality magnetic resonance contrast medium gadolinium DTPA. Physiologic saline was injected in controls. The kidneys were fixed by perfusion and the specimens were analyzed semiquantitatively by two independent observers blinded to the treatment. A statistically significant (P less than .01) cytoplasmic vacuolization was noticed in the proximal convoluted tubule cells 2 hours after injection of 3 g I/kg of diatrizoate or iopromide. Iohexol and iotrolan induced an even more significant (P less than .01) and longer-lasting vacuolization, but gadolinium DTPA did not produce lysosomal alterations. Although the vital cell organelles remained intact, reversible lysosomal alterations may represent the first structural signs of a threatening cellular injury.     

Contrast media-induced renal tubular vacuolization after dehydration. A light and electron microscopic study in rats.

Morphologic studies on the effect of dehydration on contrast media (CM)-induced renal changes were done. Sixty-six healthy Wistar rats were deprived of water for 24 hours before the intravenous (i.v.) injection of 1.0 or 3.0 g iodine (I)/kg of high-osmolal diatrizoate, low-osmolal iopromide or iohexol, iso-osmolal iotrolan, or 0.2 or 0.6 g/kg of high-osmolal magnetic contrast agent, gadolinium-DTPA (Gd-DTPA). Control animals received physiologic saline. After 2 hours, the kidneys were fixed by perfusion for light and electron microscopy, and the morphologic changes were semi-quantitatively reviewed by two independent observers blinded to the treatment. The smaller dose of iohexol or iotrolan and the larger dose of all the CM induced in the proximal convoluted tubule (PCT) cells a statistically highly significant (P less than .001) or significant (Gd-DTPA; P less than .01) cytoplasmic vacuolization. The changes were most prominent (P less than .001) after treatment with iohexol and iotrolan. The results might be related to the higher urinary CM concentration after low- and iso-osmolal agents. Dehydration further potentiates higher CM concentration. The morphologic injury, when compared with the author's earlier findings on normal rats, was clearly intensified by dehydration.     

Contrast media-induced ventricular fibrillation. A comparison of Hypaque-76, Hexabrix, and Omnipaque

Contrast media occasionally produce ventricular fibrillation during coronary angiography. We compared the fibrillatory propensity of the conventional ionic contrast medium, Hypaque-76 (H76) to the low osmolar ionic dimer Hexabrix (HB) and to the nonionic agent Omnipaque (OM) in 20 open chest anesthetized dogs. Intracoronary injection of 6 mL of contrast medium produced spontaneous ventricular fibrillation in four of ten dogs with H76, compared with two of ten with HB, and zero of ten with OM (P = .07). The induction of two premature beats by programmed stimulation of the myocardium during injection of 4 mL of contrast medium produced ventricular fibrillation in ten of ten dogs with H76, compared with three of ten with HB, and zero of ten with OM (P less than .001). Both H76 and HB produced ventricular fibrillation in ten of ten dogs when three premature beats were induced, compared with two of ten dogs with OM (P less than .001). Four mL H76 produced a 109 +/- 18 msec increase in the QT interval, compared with an 82 +/- 17 msec increase with HB, and a 45 +/- 12 msec increase with OM. We conclude that both low osmolar HB and OM are less fibrillatory than the conventional ionic medium H76, and that the nonionic medium OM is less fibrillatory than the ionic dimer contrast medium HB.     

介入诊疗对心血管病患者外周淋巴细胞DNA的损伤

目的探讨心血管病介入诊疗中的X线电离辐射对心血管病患者DNA损伤的影响。方法收治接受心血管病介入诊疗患者244例,按介入术式不同分为四组:经皮冠状动脉造影术组87例,经皮冠状动脉介入术组72例,射频消融术组48例,起搏器植入术组37例。分别于术前、术后2 h、24 h抽取患者外周血,检测外周血淋巴细胞染色体微核。同时记录患者手术全程辐射的累积皮肤表面入射剂量(CD)、面积剂量乘积(DAP)、透视时间(FT)等,观察各种介入诊疗中患者接受的辐射损伤程度和差异。结果经皮冠状动脉支架置入术组CD和DAP值显著高于其他三组,而其他三组间CD和DAP值差异无统计学意义(P>0.05)。患者术后2 h染色体微核率为16.3‰±4.2‰,P<0.05),术后24 h为17.5‰±5.1‰,,明显高于术前水平(13.8‰±4.7‰,P<0.05)。结论不同介入术中,患者接受的辐射剂量不同,但介入诊疗中的电离辐射都可能会造成患者的DNA损伤。     

Relationships between clonogenic cell survival,DNA damage and chromosomal radiosensitivity in nine human cervix carcinoma cell lines

Purpose : To compare clonogenic cell survival, DNA damage and chromosomal radiosensitivity in nine cervix carcinoma cell lines. Materials and methods : Initial and residual (after 24h repair) radiation-induced DNA damage was evaluated using pulsed field gel electrophoresis. Chromosome damage was measured by micronucleus (MN) induction in cytochalasin-B-induced binucleate cells. Results : Significant differences between the cell lines were obtained in the induced levels of initial damage, residual damage and MN. Values for SF2 for the nine cell lines ranged from 0.36 to 0.92. No correlation was found between clonogenic measurements of radiosensitivity and initial DNA damage dose-response slopes. However, borderline significant correlations were seen between clonogenic radiosensitivity data and the levels of residual DNA damage. There was no correlation between clonogenic radiosensitivity and the levels of radiation-induced MN. Cell lines with high levels of initial damage had high yields of MN induced by radiation and the correlation seen was significant. Conclusions : The poor correlation between the different endpoints precludes their use in a clinical setting on primary tumour samples in vitro. It may be that tumour cell lines in vitro are a poor model for tumours in vivo. Studies aimed at assessing assays for measuring tumour radiosensitivity therefore should employ clinical samples. In vitro cell line work should concentrate on unravelling the complex mechanisms involved in determining a radiosensitive or radioresistant phenotype.     

Contrast agent distribution in microvascular damage of infarcted pig myocardium

Purpose: We determined whether reperfusion damage was sufficient to allow extravasation of a large molecular weight contrast agent into infarcted pig myocardium.Material and Methods: Five pig hearts were subjected to in situ occlusion of the left anterior descending coronary artery (2 h) followed by reperfusion (1 h). The hearts were excised and perfused in the Langendorff mode for ex vivo MR imaging. Polylysine-Gd-DTPA (50,000 Da) and Gd-DTPA (500-700 Da) were injected into the aorta (alternately) and followed by measurements of T1 relaxation and mean transit time (MTT).Results: In the normal myocardium, MTT of Gd-DTPA (56.8±23.2 s) was significantly (p=0.02) longer than that of polylysine-Gd-DTPA (29.0±7 s). However, both normal and infarcted myocardium showed similar MTT (29.0±7.0 vs. 28.0±5.0 s, p>0.05) when using polylysine-Gd-DTPA.Conclusion: The results indicate that the permeability of capillaries to polylysine-Gd-DTPA was not significantly higher in infarcted regions of the myocardium compared to normal tissue. However, infarcted myocardium displayed an increased permeability to the small molecular weight Gd-DTPA. We conclude that microvascular damage may not be sufficient to allow the extravasation of polylysine-Gd-DTPA in infarcted myocardium.     

Relationships between clonogenic cell survival, DNA damage and chromosomal radiosensitivity in nine human cervix carcinoma cell lines

PURPOSE: To compare clonogenic cell survival, DNA damage and chromosomal radiosensitivity in nine cervix carcinoma cell lines. MATERIALS AND METHODS: Initial and residual (after 24h repair) radiation-induced DNA damage was evaluated using pulsed field gel electrophoresis. Chromosome damage was measured by micronucleus (MN) induction in cytochalasin-B-induced binucleate cells. RESULTS: Significant differences between the cell lines were obtained in the induced levels of initial damage, residual damage and MN. Values for SF2 for the nine cell lines ranged from 0.36 to 0.92. No correlation was found between clonogenic measurements of radiosensitivity and initial DNA damage dose response slopes. However, borderline significant correlations were seen between clonogenic radiosensitivity data and the levels of residual DNA damage. There was no correlation between clonogenic radiosensitivity and the levels of radiation-induced MN. Cell lines with high levels of initial damage had high yields of MN induced by radiation and the correlation seen was significant. CONCLUSIONS: The poor correlation between the different endpoints precludes their use in a clinical setting on primary tumour samples in vitro. It may be that tumour cell lines in vitro are a poor model for tumours in vivo. Studies aimed at assessing assays for measuring tumour radiosensitivity therefore should employ clinical samples. In vitro cell line work should concentrate on unravelling the complex mechanisms involved in determining a radiosensitive or radioresistant phenotype.     

Opiate involvement in contrast media-induced blood pressure changes

The intravenous administration of contrast media (CM) often alters blood pressure (BP). Osmolality plays a role, but the magnitude and even direction of change varies under similar (osmotic) conditions, indicating the involvement of other mechanisms. Male Wistar rats, anesthetized with pentobarbital, received sodium/meglumine diatrizoate, iohexol, or normal saline, 4 ml/kg, via a tail vein, while blood pressure was recorded continuously. Additional groups were pretreated with the opiate antagonist, naloxone (1 mg/kg, IV), or with an equal volume of normal saline 5 minutes prior to the diatrizoate injection. Comparisons of BP change were made with the Student's t-test. Diatrizoate caused a significant (P less than .0002) increase in BP relative to the saline control group, iohexol did not. Thus, the increase with diatrizoate was significantly greater than with iohexol (P less than .00006). Neither the saline nor naloxone pretreatment altered BP significantly. Saline pretreatment did not alter the significant increase in BP produced by the diatrizoate. However, the diatrizoate-induced increase in BP was prevented by the naloxone pretreatment and was significantly less than after the saline pretreatment (P less than .0001). Based on these and previous results, the authors hypothesize that release of endogenous opioids may play a role in BP changes caused by intravenous CM and that significant CM-induced changes may be prevented pharmacologically with the selective opiate blocker, naloxone.     

Low folate status increases chromosomal damage by X-ray irradiation

PURPOSE: To examine how folate status influences chromosomal damage following X-ray irradiation. MATERIAL AND METHODS: In an animal study, mice were fed either a low, basal, or high folic acid diet (0, 2, or 40 mg/kg diet, respectively) for 4 weeks, and then given total body irradiation (TBI) at 0.5 Gy. In a human study, subjects were supplemented with folic acid (800 microg/day) for 2 weeks and their peripheral blood was irradiated at 0.5 Gy in vitro. Chromosomal damage was determined by micronucleus assay. RESULTS: In an animal study, TBI-induced chromosomal damage was higher and folate concentration was lower in the bone marrow of the low folic acid group compared to the other two diet groups. The chromosomal damage and folate concentration were comparable between the basal and high folic acid groups. TBI administered to mice decreased folate in the plasma, erythrocyte and bone marrow. In a human study, supplementation with folic acid increased plasma folate, but did not influence either plasma homocysteine or X-ray-induced chromosomal damage in lymphocytes. CONCLUSION: Low folate status increases susceptibility to X-ray-induced chromosomal damage, but excessive folic acid supplementation under normal conditions yields no further protection due to folate saturation in the target tissue.     

Low folate status increases chromosomal damage by X-ray irradiation

Purpose: To examine how folate status influences chromosomal damage following X-ray irradiation.

Material and methods: In an animal study, mice were fed either a low, basal, or high folic acid diet (0, 2, or 40 mg/kg diet, respectively) for 4 weeks, and then given total body irradiation (TBI) at 0.5 Gy. In a human study, subjects were supplemented with folic acid (800 μg/day) for 2 weeks and their peripheral blood was irradiated at 0.5 Gy in vitro. Chromosomal damage was determined by micronucleus assay.

Results: In an animal study, TBI-induced chromosomal damage was higher and folate concentration was lower in the bone marrow of the low folic acid group compared to the other two diet groups. The chromosomal damage and folate concentration were comparable between the basal and high folic acid groups. TBI administered to mice decreased folate in the plasma, erythrocyte and bone marrow. In a human study, supplementation with folic acid increased plasma folate, but did not influence either plasma homocysteine or X-ray-induced chromosomal damage in lymphocytes.

Conclusion: Low folate status increases susceptibility to X-ray-induced chromosomal damage, but excessive folic acid supplementation under normal conditions yields no further protection due to folate saturation in the target tissue.     

Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship

Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of ¹³¹I (259–3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean±SD) were 3.19±0.93, 10.83±1.72 and 5.75±2.06, respectively, in the whole group, and these values differed significantly from each other (P<0.001). In order to perform a quantitative evaluation of the present data and a comparative analysis with the results of previous studies reported in the literature, we defined acute and late effects using a damage ratio (DR) and a recovery ratio (RR), based on the basal, acute and late data for individual patients. No statistically significant difference was found in the DR between DTC and TTX patients (76.4%±11.5% vs 67.6%±9.0%), while the mean RR was higher in TTX patients than in the DTC group (75.2%±24.4% vs 36.8%±13.7%). The DR on the 3rd day was not related to the administered ¹³¹I dose in the whole group, but a negative correlation was found between the ¹³¹I dose and the RR at the 6th month (r=–0.60, P=0.04). The best fit for this relationship was obtained by a linear-quadratic model, as y=104.89x–28.4x²+38.1 (R²=0.51, P=0.04). On the other hand, comparative analysis with the results of previous studies with comparable sampling times revealed that the best fit for the relationships between the administered dose of ¹³¹I and DR and RR were obtained with a linear-quadratic model (Y=D+D²) rather than a linear one. However, there was an interesting difference in comparison with in vitro studies, in that we found the coefficient to have a negative value, suggesting the disappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following ¹³¹I treatment. Further studies are therefore needed to clarify the effect of the negative value on the biological dosimetry approach in continuous internal low LET radiation, as in the case of ¹³¹I treatment.     

Heritability of chromosomal radiosensitivity in breast cancer patients: a pilot study with the lymphocyte micronucleus assay

Of breast cancer patients, 30% are sensitive in a lymphocyte assay of radiation-induced chromosome damage (micronucleus induction) compared with 10% of healthy controls. Twenty-two first-degree relatives of 11 sensitive patients had an average micronucleus yield significantly higher than that of 68 controls. This suggests that radiosensitivity in this assay may be an inherited characteristic associated with predisposition to breast cancer.     

Heritability of chromosomal radiosensitivity in breast cancer patients: a pilot study with the lymphocyte micronucleus assay

Of breast cancer patients, 30% are sensitive in a lymphocyte assay of radiation-induced chromosome damage (micronucleus induction) compared with 10% of healthy controls. Twenty-two first-degree relatives of 11 sensitive patients had an average micronucleus yield significantly higher than that of 68 controls. This suggests that radiosensitivity in this assay may be an inherited characteristic associated with predisposition to breast cancer.