Aspirin and fraxiparine in the prevention of laser induced thrombosis in the presence of iodinated contrast media

The purpose of this study was to investigate the thromboembolic properties of ionic and nonionic contrast media in rats pretreated with aspirin and/or fraxiparine using an experimental model of laser induced thrombosis in the mesenteric microvessels of 17 groups of five male Wistar rats each. Two ionic (ioxaglate and diatrizoate) and two nonionic contrast media (iopamidol and iohexol), alone or associated with antithrombotic drugs (aspirin and/or fraxiparine) were studied. To evaluate the effects of these substances in this model, the number of laser beams needed to induce platelet thrombus formation, the number of emboli detached from the thrombus and the duration of embolization were quantified. Platelet aggregation induced by ADP, induced hemorrhagic time (IHT) and haemoglobin loss level were also determined. Both contrast media injected at 3 ml/kg caused a significant increase in the number of emboli and the duration of embolization (p<0.05). Pretreatment with aspirin and/or fraxiparine in the presence of ionic contrast media showed antithrombotic activities equal to those obtained when they were tested alone (p<0.05), while in the presence of nonionic contrast media, these drugs only neutralised the prothrombotic effects. There were no differences with the NaCl treated group (p>0.05). The ionic contrast media, and to a lesser extent the nonionic contrast medium: iohexol, inhibited platelet aggregation, while iopamidol behaved as an activator. The antithrombotic drugs tested in this study prevent the prothrombotic activities of contrast media therefore suggesting their use before radiographic procedures.     

Liver toxicity of diatrizoate and a non-ionic contrast medium (C29). Coeliac angiography in the rabbit

Toxic effect on the liver of diatrizoate and a new non-ionic contrast medium (C29) were investigated using coeliac angiography in rabbits. The contrast media were injected in doses of 5 ml/kg rabbit with a concentration of 370 mg I/ml. Serum levels of ALAT, ASAT, ALP and bilirubin did not change significantly after the injections.     

Delayed-type hypersensitivity to a nonionic, radiopaque contrast medium

BACKGROUND: True allergic reactions to iodinated radiocontrast media are rare, and only a few well-documented cases of delayed-type hypersensitivity reactions caused by contrast media have been described. METHODS: We report a 61-year-old patient in whom percutaneous transluminal coronary angioplasty (PTCA) was performed with iopamidol, a nonionic contrast medium. Seven days later, the patient developed generalized maculopapular exanthema. Repeated patch tests with several iodinated agents were performed. RESULTS: A first patch test with iopamidol was positive. Repetition of the patch tests showed positive results to iopamidol as well as to iohexol and ioversol, two other nonionic contrast media, but not to other iodinated substances. Three months later, PTCA was repeated, and iopamidol was used again. Despite premedication, pruritic macular exanthema developed 1 day later. Whether iopamidol or trometamol -- an additive substance in the contrast medium -- was causative could not be determined, since a third set of patch tests was negative. CONCLUSIONS: Delayed-type hypersensitivity reactions to iodinated contrast media are rare. We recommend that patients with delayed exanthematous reactions undergo patch or intradermal tests with different contrast media and their additives, and that readings be performed immediately and later at days 2 and 3.     

The effect of radiographic contrast media on human vascular smooth muscle cells

The relation between intravascular radiographic contrast media (RCM) and myointimal hyperplasia after percutaneous transluminal angioplasty is not known. We have investigated the cytotoxic effects of RCM on human vascular smooth muscle cells (VSMCs) and their effect on the growth of these cells. The cytotoxic effects of RCM were studied using human VSMCs. The cells after being grown to confluency were exposed for 60 min to 250 mgI ml-1 of diatrizoate, ioxaglate, iopromide, iotrolan and saturated mannitol solutions. The control group was treated with only 15% fetal calf serum (FCS) containing medium. The viability of the cells was examined using the trypan blue exclusion test. The effect of RCM on growth was assessed by exposing the VSMCs after growth arrest, for either 15 or 60 min to 250 mgI ml-1 of diatrozoate, ioxaglate, iopromide, iotrolan and saturated mannitol solution. There was no significant change in the viability of the VSMCs after 60 min exposure to iopromide, iotrolan, saturated mannitol solution, and after 15 min exposure to diatrizoate or ioxaglate. After exposure to diatrizoate or ioxaglate for 60 min, 16.5 +/- 2.2% or 9.2 +/- 2.6% dead cells were found, respectively (p < 0.05 versus control). In the growth assay of VSMCs, diatrizoate, ioxaglate and saturated mannitol solutions reduced the growth rate (p < 0.05 versus control). No significant change was observed with iopromide and iotrolan. In conclusion, ionic RCM have cytotoxic and cytostatic effects on VSMCs while non-ionic media have no effects. There is no direct stimulatory effect of contrast media on the growth of VSMCs. The cytotoxic and cytostatic effects of contrast media seems to be both osmolality and chemotoxicity dependent. Low osmolar non-ionic RCM are not likely to contribute to the mechanisms responsible for myointimal hyperplasia after angioplasty.     

Complex segregation analyses: uses and limitations

It is sometimes difficult to visualize the luminal borders of the vessel even by intracoronary ultrasound (ICUS), especially after coronary intervention. In this study, we evaluated the potential for improving visualization at intervention sites using contrast-enhanced ICUS and the suitable contrast agents for this procedure in humans. In 37 patients, ICUS (30 MHz) was performed with intracoronary injection (3 ml) of 7 different contrast preparations and without the contrast agents (control) after coronary intervention. The contrast agents used were as follows: saline solution, standard iomeprol, standard ioxaglate, sonicated iomeprol, sonicated ioxaglate, 50% Albunex, and 100% Albunex. Vessel wall delineation, contrast homogeneity (Grade 0-3), peak contrast intensity and shadowing were examined. Homogeneous and complete opacification of the vessel lumen and false lumen was observed with sonicated ioxaglate, 50% and 100% Albunex. Shadowing was not observed at all with sonicated ioxaglate and was uncommon with 50% Albunex, whereas 100% Albunex caused shadowing in all cases. The coronary delineation rate with the other contrast agents was only 50-70 %, and the homogeneity and peak intensity were relatively low. Thus, sonicated ioxaglate and 50 % Albunex both achieved good visualization, but the former is cheaper, stable and takes shorter to prepare. Large dissection in 5 patients were found by contrast-enhanced ICUS' whereas they were not detected by coronary angiography. All of them needed additional interventional therapy due to the results of contrast-enhanced ICUS. In conclusion, contrast-enhanced ICUS is useful for evaluation of the results by intervention therapy, and of the agents we studied sonicated ioxaglate is best for contrast-enhanced ICUS.     

Bronchoconstrictor and respiratory effects of neurokinin A in dogs

Neurokinin A (NKA) is the primary bronchoconstrictor tachykinin in the lungs of several species, including humans and has been implicated as an important mediator of inflammatory lung disorders, such as asthma. In this study, we investigated the effect of NKA on airway mechanics (lung resistance, dynamic lung compliance) and respiration (tidal volume, respiratory rate) in anesthetized, spontaneously breathing, male beagle dogs. The dogs were challenged with aerosolized NKA that was delivered from a jet nebulizer to the airways through an endotracheal tube. The challenge consisted of five separate inflations of 600 ml of air/inflation over a 1-min period. Challenge with aerosolized NKA (0.1-1%) produced a dose-dependent increase in lung resistance and a decrease in dynamic lung compliance. The bronchoconstriction induced by 1% NKA peaked at 0.5 min after challenge and had a duration of approximately 5 min. Challenge with 1% NKA also reduced tidal volume and increased respiratory rate. Pretreatment of dogs with the NK-2 receptor antagonist, SR 48968 dose-dependently (1-10 mg/kg, p.o.) blocked the bronchoconstriction and respiratory responses to NKA challenge. Pretreatment with the NK1-receptor antagonist, CP 99994 (1 mg/kg, i. v.) had no effect on the increase in lung resistance and the decrease in dynamic lung compliance due to NKA challenge, but blunted the respiratory response to NKA. Pretreatment of dogs with inhaled ipratropium bromide (0.01%) slightly, but significantly reduced the increase in lung resistance due to NKA challenge but had no effect on the decrease of dynamic lung compliance or on the respiratory responses to NKA. As expected, the bronchoconstrictor response to inhaled methacholine was completely blocked by inhaled ipratropium bromide (0.01%). In conclusion, we have identified an NK2-receptor mediated bronchoconstrictor effect of NKA in dogs. Cholinergic reflexes play a small, but significant role in this response. Furthermore, both NK1 and NK2-receptors appear to be involved with the development of the rapid, shallow breathing response to NKA challenge. These results demonstrate an effect of tachykinins on airway mechanics and ventilatory reflexes in dogs.     

Cultured human airway smooth muscle cells stimulated by interleukin-1beta enhance eosinophil survival

Airway smooth muscle may be an important cellular source of proinflammatory mediators and cytokines and may participate directly in airway inflammation. In this study we have examined whether airway smooth muscle cells could contribute to mechanisms of eosinophil accumulation by prolonging their survival. To investigate this possibility, conditioned medium from human airway smooth muscle cells stimulated with interleukin (IL)-1beta was examined on the in vitro survival of highly purified human peripheral blood eosinophils. After 7 d, when cultured in control medium, less than 1 +/- 0.2% of the initial eosinophil population remained viable. In contrast, culture in medium conditioned for 96 h by human airway smooth muscle cells stimulated with IL-1beta (1 pg-100 ng/ml) resulted in a concentration-dependent increase in eosinophil survival. (The concentration that produced 50% of this effect was 0.03 ng/ml IL-1beta.) Maximum eosinophil survival occurred at 1 to 3 ng/ml IL-1beta. This effect was also time-dependent and was readily detected in airway smooth muscle cell-conditioned medium after just 3 h of stimulation with IL-1beta (1 ng/ml). It continued to increase before reaching a plateau around 24 h, with no decrease in activity for up to 120 h of stimulation. Conditioned medium from unstimulated airway smooth muscle cells did not enhance eosinophil survival. The survival-enhancing activity was completely inhibited (the concentration that inhibited 50% [IC50] was 6.9 microg/ml) by a polyclonal goat antihuman antibody to granulocyte-macrophage colony stimulating factor (GM-CSF) (0.3-100 microg/ml), but antibodies (10-100 microg/ml) to IL-3 and IL-5, and a normal goat immunoglobulin G control had no effect on the eosinophil survival-enhancing activity. GM-CSF levels in culture medium from smooth muscle cells were markedly increased by IL-1beta and were maximum at 30 ng/ml (0.037 ng/ml/10(6) cells versus 3.561 ng/ml/10(6) cells, unstimulated versus 30 ng/ml IL-1beta). The IL-1 receptor antagonist inhibited both the production of GM-CSF (IC50 19. 1 ng/ml) and the eosinophil survival-enhancing (IC50 53.7 ng/ml) activity stimulated by IL-1beta. Release of GM-CSF elicited by IL-1beta was inhibited by dexamethasone but not by indomethacin. These data indicate that cultured human airway smooth muscle cells stimulated with IL-1beta support eosinophil survival through production of GM-CSF and thus may contribute to the local control of inflammatory cell accumulation in the airways.     

Transport of amino acid aryl amides by the intestinal H+/peptide cotransport system, PEPT1

The oxygen tension (PO2) in the renal cortex and outer renal medulla in 26 rats was studied by use of oxygen microelectrodes before and after injection of x-ray contrast media (CM). The CM, iopromide, ioxaglate and iotrolan were administrated intravenously in iodine equivalent doses (1,600 mg iodine/kg body wt). Ringer's solution was used as the control. In the outer medulla, all three CM induced a decrease in PO2: iopromide (N = 6) from 30 +/- 3 to 18 +/- 4 mm Hg; ioxaglate (N = 7) from 32 +/- 6 to 15 +/- 4 mm Hg; and iotrolan (N = 6) from 36 +/- 3 to 14 +/- 4 mm Hg. All these decreases were significant. After the injection of Ringer's (N = 7) there was an increase from 34 +/- 3 to 35 +/- 3 mm Hg. In the cortex a slight decrease was noted for injection of CM, but this was significant only after injection of iotrolan. All tested contrast media decrease PO2 in the outer renal medulla, which may partly explain contrast medium-induced acute renal failure.     

HIV/AIDS-related behavior change among injecting drug users in different national settings

1. The ability of airway epithelial cells to produce insulin-like growth factor I may be important in the pathogenesis of subepithelial fibrosis observed in the airways of patients with asthma. We determined whether human airway epithelial cells are capable of producing polypeptide mediators that could induce fibroblast proliferative activity, in particular insulin-like growth factor I. 2. We examined 12 primary cultures of human airway epithelial cells grown to confluence on collagen gel-coated dishes. Using a colorimetric assay based on the uptake and subsequent release of Methylene Blue, increased proliferation of human fetal lung fibroblasts was detected in conditioned media from airway epithelial cells. The median stimulation of fibroblast proliferation was 49.9% (range 25.6-113.3%) above control values (observed at 1:2 dilution of media). 3. A neutralizing antiserum to insulin-like growth factor I partly inhibited fibroblast proliferation induced by epithelial cell conditioned media by 52.2% (49.9-109%; n = 5). 4. Radioimmunoassay for insulin-like growth factor I in conditioned media demonstrated a median concentration of 54.1 ng/ml (32.4-96.8 ng/ml). 5. Insulin-like growth factor I mRNA was detected in epithelial cell monolayers by Northern blot analysis using an insulin-like growth factor I cDNA probe. 6. The insulin-like growth factor I gene is expressed in cultured human airway epithelial cells, which also secrete insulin-like growth factor I protein. Insulin-like growth factor I also accounts for the major mitogenic activity for fibroblasts of cultured human epithelial cell conditioned media. Insulin-like growth factor I may function in a paracrine manner to modulate fibroblast behaviour and may be involved in airway processes, such as those occurring in asthma.     

Histamine release and contrast media-induced renal vasoconstriction

RATIONALE AND OBJECTIVES: The authors' purpose was to investigate the role of histamine release causing renal vasoconstriction induced by application of contrast media, an important element in contrast medium-induced nephrotoxicity. MATERIALS AND METHODS: Isometric contractions in rabbit segmental renal arteries stimulated with KCl and increasing concentrations of the ionic contrast medium diatrizoate and the nonionic agents iomeprol and iodixanol were studied both with and without increasing concentrations of the histamine H1 and H2 blockers diphenhydramine and cimetidine. Histamine concentrations after contrast medium application were determined. RESULTS: Contrast-induced, dose-dependent, reversible renal artery contractions of 27%, 4.5%, and 5% of the control KCl contraction were found for diatrizoate, iodixanol, and iomeprol respectively. Those induced by the ionic contrast medium were statistically significantly higher (P < .01). Contractions were partially inhibited by diphenhydramine (49%) but not by cimetidine. Significant elevation of histamine concentrations (P < .05) was detected only after stimulation with diatrizoate but not with nonionic agents. CONCLUSION: Ionic contrast medium induces histamine release leading to renal vasoconstriction, which can be partly blocked by H1 blockers. Histamine has no effect on renal vasospasm induced by nonionic contrast media.     

Frequency and effects of extravasation of ionic and nonionic CT contrast media during rapid bolus injection

PURPOSE: To determine the frequency and clinical effects of extravasation related to rapid bolus infusion of ionic and nonionic contrast media. MATERIALS AND METHODS: Records of 5,106 computed tomographic studies in adult patients who underwent mechanical bolus injection of contrast medium through a plastic cannula in an upper extremity were retrospectively reviewed. RESULTS: Mean infusion rate was 2.8 mL/sec (range, 1-5 mL/sec). Extravasation occurred in 48 (0.9%) patients, including in four of 928 patients who received the median injection rate (2.5 mL/sec). Injection rate was not correlated with frequency or amount of extravasation. Average age and use of ionic versus nonionic contrast medium were identical in patients with and in those without extravasation. There was no sex difference. Thirty-one patients had extravasation of ionic contrast medium; nine of these had extravasation of at least 50 mL. Seventeen patients had extravasation of nonionic contrast medium; seven of these had extravasation of at least 50 mL. Hyaluronidase infiltration was often used as treatment for larger extravasations (in 10 patients each with extravasation of ionic or nonionic medium). No patient required surgical intervention, and none had severe or permanent long-term effects. CONCLUSION: The frequency of extravasation of contrast medium after mechanical bolus injection is higher than that reported for hand-injection or drip-infusion techniques, but there is no correlation between injection rate and extravasation frequency.     

Carbon dioxide as a contrast agent to guide vascular interventional procedures

OBJECTIVE: The purpose of this study was to assess the value and limitations of carbon dioxide (CO2) as a contrast agent to guide vascular interventional procedures. SUBJECTS AND METHODS: Twenty-two adults underwent 26 vascular interventional procedures (21 arterial, five venous). We aimed to use only CO2 if possible because these patients had renal insufficiency (n = 21; mean creatinine level, 2.8 mg/dl) or were allergic to contrast material (n = 1). Arterial procedures performed included renal angioplasty or stent (n = 6), iliac angioplasty or stent (n = 5), infrainguinal angioplasty (n = 5), arterial bypass graft angioplasty (n = 3), and thrombolysis (n = 2). Venous procedures included transjugular intrahepatic portosystemic shunt recanalization (n = 3), angioplasty of the venous anastomosis of a thigh dialysis graft (n = 1), and angioplasty of the inferior vena cava (n = 1). RESULTS: Twenty-five of the 26 procedures were successfully performed. Of the 26 procedures, eight required no iodinated contrast material and 11 required less than or equal to 20 ml of contrast material. CO2 proved to be inadequate for the remaining seven procedures. Iliac artery angioplasty or stent placement required an average of 9 ml of iodinated contrast material; infrainguinal angioplasty required an average of 22 ml of iodinated contrast material. CONCLUSION: CO2 can be successfully used as a contrast agent in a variety of vascular interventional procedures. Such procedures can usually be performed in the iliac and infrainguinal arteries using minimal supplemental iodinated contrast material. However, CO2 failed to provide satisfactory guidance in half of the intraabdominal procedures in our study.     

Influence of sonographic contrast media on microcirculation in rats

In an open placebo-controlled study the influence of the injection of different sonographic contrast media on the microcirculation was proved. The study was performed in 7 Sprague-Dawley rats. In order to examine this query two different sonographic contrast media in comparison to agitated electrolyte solution (as the placebo) were injected into the abdominal aorta of 7 anaesthetized rats as a 2 ml/kg bolus at 10-min intervals. Examined were a newly developed agitated ultrasound solution (AK I: an aequeous solution of a vegetable phospholipid) and a radiographic contrast agent (AK II: 741 mg Ioversol or 350 mg iodine, respectively, per ml) which is used in an agitated form as ultrasound contrast agent, too. 1 min before and until 2 min after each injection the capillary perfusion of the same vessel area in the major omentum was measured (video-recording by use of intravital microscopy). The erythrocyte velocity was determined off-line by an image analysing system. Whereas the agitated X-ray contrast medium AK II decreases the mean capillary perfusion (temporary flow stagnation in single capillaries), AK I as well as agitated electrolyte solution did not influence the capillary erythrocyte velocity in the major omentum. The gaps which appeared immediately after the injection of AK I seem to have been brought about by spherosomes of AK I. Still the spherosomes are so small that they can pass through the capillaries, or if they are larger which cannot be determined using in vivo microscopy the flow force necessary for the deformation of the bubbles is so small that the capillary perfusion is not influenced. The injection of agitated AK I does not lead to significant changes of the microcirculation.     

In vitro evaluation of contrast medium concentration and depth effects on the radiographic appearance of specific canine urolith mineral types

Nine pure mineral types of canine uroliths (bladder or urethral origin only) identified in a chronologic sample from the Minnesota Urolith Center were compared to sequential dilutions of iodinated radiographic contrast medium in vitro. The uroliths studied were those composed of 100% magnesium ammonium phosphate, calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate appatite, calcium hydrogen phosphate dihydrate (brushite), ammonium acid urate, sodium acid urate, cystine, and silica. The radiopacity of the uroliths was classified as radiolucent, isopaque, or radiopaque, as compared to the radiopacity of the contrast medium solutions in which they were placed, using 2.0 mm and 5.0 mm depths in petri dishes radiographed using a table-top technique. A statistically significant relationship was found between the effective atomic number of the uroliths and the effective atomic number of the contrast medium solutions to which they were compared for the endpoints of isopacity, first lucency (in increasing iodine concentration sequence), and optimal visualization of internal architecture. In general, uroliths isopaque or radiolucent in contrast medium solutions weaker than 23.5 mgI2/ml are most likely ammonium acid urate or sodium acid urate. Uroliths isopaque or radiolucent in contrast medium solutions between 23.5 mgI2/ml and 44.4 mgI2/ml are probably magnesium ammonium phosphate, cystine, or silica. Uroliths that remained radiopaque in solutions stronger than 44.4 mgI2/ml, and particularly those radiopaque in contrast medium solutions stronger than 80 mgI2/ml, almost always contained calcium. This relative opacity assessment is proposed for use in double contrast cystography as an aid in differentiating urolith mineral types clinically to facilitate appropriate use of medical protocols to dissolve uroliths or to prevent their growth or recurrence.     

Bronchial hyperresponsiveness after cervical spinal cord injury

Cervical spinal cord injury results in interruption of sympathetic airway innervation, which originates from the upper thoracic spine, whereas parasympathetic nerve supply, arising in the vagal nuclei of the brainstem, remains intact. To assess the effect of such an altered neural environment on airway reactivity, bronchoprovocation testing was performed on eight subjects with nonacute traumatic lesions of the cervical spine, all of whom were lifetime nonsmokers without history of respiratory symptoms prior to their injury. Bronchial challenge was subsequently repeated after pretreatment with the anticholinergic agent, ipratropium bromide, an inhibitor of airway muscarinic receptors. All subjects demonstrated hyperresponsiveness to methacholine (the concentration of methacholine producing a fall in FEV1 of 20 percent from baseline [PC20] = 1.42 +/- 1.61 [SD] mg/ml). Airway hyperreactivity was completely blocked by pretreatment with inhaled ipratropium bromide (mean PC20 > 25 mg/ml [p < 0.0001]). The bronchial hyperresponsiveness observed in this population most likely reflects the loss of sympathetic airway innervation and resultant unopposed cholinergic bronchoconstrictor tone which results from transection of the cervical spine. Blockade of methacholine hyperresponsiveness with ipratropium bromide suggests a muscarinic receptor-mediated phenomenon.     

Analysis of the factors influencing the osmolality of eight monomeric nonionic iodinated contrast medium molecules

RATIONALE AND OBJECTIVES: Because the measured osmolality of a contrast medium solution differs considerably from the theoretical one, the author analyzed the relative influence of various parameters on the experimental osmolality and derived an equation permitting the prospective calculation of the real osmolality of monomeric nonionics. The author discusses the consequences of the results. MATERIALS: Eight monomer nonionic iodinated molecules (ioversol, iohexol, P-569, iobitridol, P-530, iopamidol, and iopromide) were analyzed. A parameter combining the hydrophilic and the hydrophobic aspects of these molecules was calculated, the relative weight of each composing term was calculated with the multiple nonlinear regression technique. RESULTS: The regression equation was determined based on seven compounds. A high proportion of explained variance was achieved. The prediction for ioxilan (with the lowest osmolality of the eight molecules) yielded a good result, confirming that structural influences determine the osmolality of a molecule. CONCLUSIONS: The study of the parameters influencing the osmolality of eight nonionic iodinated monomer contrast medium molecules led to the development of a regression equation. It is shown that both the hydrophilic and hydrophobic characteristics of a molecule are important in the determination of the osmolality. This equation can be useful prospectively.     

Deep vein thrombi associated with the use of plastic ankle-foot orthoses

Gadopentetate dimeglumine (Gd-DTPA) is widely used as a contrast agent in MR imaging. We report on a case in which Gd-DTPA was used as the contrast agent during angioplasty in a patient who had recently had an adverse reaction to a non-ionic iodinated contrast medium. Gd-DTPA allowed a diagnostic angiogram to be performed with no side effects, and may thus be a useful contrast agent at angioplasty in patients with contra-indications to iodinated contrast media.     

Cholangiographic excretion studies: a comparison of iodipamide and iodoxamate in the dog

Iodoxamic acid is a new hexaiodinated cholegraphic contrast agent. The methylglucamine salts of iodoxamate and iodipamide were administered to labrador dogs as an intravenous infusion. Bile salts were also infused. The biliary concentration and output of the two agents were compared. Bile flow rate, bile salt concentration and bile salt output with the two agents were also compared. The biliary output of iodoxamate (0.70-0.78 mumol/min/kg) was more than 50% higher than the iodipamide output (0.46 mumol/min/kg). Bile salt output and concentration with iodoxamate infusion were lower than with iodipamide infusion. The bile flow rate was higher with the new agent. The complementary effects of increased contrast output and decreased bile salt output with the new agent led to a significantly higher biliary iodine concentration compared with iodipamide. The results of this study support the suggestion that iodoxamate represents a significant advance in the cholegraphic contrast media field.     

Selective coronary artery perfusion in vitro: a method to study cardiac effects of contrast media

RATIONALE AND OBJECTIVES: The authors evaluated selective perfusion of the coronary arteries in the isolated rat heart as a model for studying contrast medium-induced cardiac effects and compared the effects of iodixanol, iotrolan, and ioxaglate with this model. MATERIALS AND METHODS: Isolated, spontaneously beating rat hearts were used. Control hearts were perfused in the Langendorff or the selective perfusion mode receiving Krebs Henseleit buffer. Contrast media were injected selectively into the left coronary artery. Left ventricular pressure and electrocardiographic parameters were monitored continuously throughout the experiments. RESULTS: The stability of the selective perfusion preparation was similar to that of the conventional Langendorff preparation. Ioxaglate (0.3 g iodine per kilogram body weight) significantly (P < .05) depressed left ventricular contractility and decreased (P < .05) left ventricular pressure. Iodixanol and iotrolan had minor cardiac effects. CONCLUSION: Selective coronary artery perfusion seems to be a suitable model for studying direct cardiac effects of contrast media. The nonionic dimers, iodixanol and iotrolan, induce only minor changes in cardiac function.     

Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses

We have hypothesized that antiallergic activity of inhaled heparin is molecular weight dependent and mediated by "nonanticoagulant fractions" (NAF-heparin). Therefore, we studied comparative effects of high-, medium-, and ultralow-molecular-weight (HMW, MMW, and ULMW, respectively) NAF-heparins on acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 23 allergic sheep, before and immediately after challenge with Ascaris suum antigen, without and after pretreatment with inhaled NAF-heparins. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units, which increased specific lung resistance by 400%. NAF-heparins attenuated ABR and AHR in a molecular-weight-dependent fashion. HMW NAF-heparin (n = 8) was the least effective agent: it attenuated ABR [inhibitory dose causing 50% protection (ID50) = 4 mg/kg] but had no effect on AHR. MMW NAF-heparin (n = 8) showed intermediate efficacy (ABR ID50 = 0.8 mg/kg, AHR ID50 = 1.4 mg/kg), whereas ULMW NAF-heparin (n = 7) was the most effective agent (ABR ID50 = 0.4 mg/kg, AHR ID50 = 0.2 mg/kg). ULMW NAF-heparin was 3.5 times more potent in attenuating antigen-induced AHR when administered "after" antigen challenge and failed to inhibit the bronchoconstrictor response to carbachol and histamine. In 15 additional sheep, segmental antigen challenge caused a marked increase in histamine in bronchoalveolar lavage fluid that was not prevented by any of the inhaled NAF-heparins. These data indicate that antiallergic activity of inhaled heparin is independent of its anticoagulant action and resides in the <2,500 ULMW chains. The antiallergic activity of NAF-heparins is mediated by an unknown biological action and may have therapeutic potential.