Potentials and limitations of low-concentration contrast medium (150 mg iodine/ml) in CT pulmonary angiography.

AIM: To assess the feasibility of producing diagnostic multidetector computed tomography (MDCT) pulmonary angiography with low iodine concentration contrast media (150 mg iodine/ml) in patients with suspected acute pulmonary embolism. MATERIALS AND METHODS: Ninety-five randomized patients underwent MDCT (64 row) pulmonary angiography with 100ml iopromide either at low concentration (LC) of 150 mg iodine/ml (n=45) or high concentration (HC) of 300 mg iodine/ml (n=50), delivered at the rate of 5 ml/s via a power injector. Two experienced radiologists, blinded to the concentration used, subjectively assessed the diagnostic quality and confidence using a four-point scale [1=poor (not diagnostic), 2=satisfactory, 3=good, 4=excellent]. Attenuation values (in HU) were measured in the main proximal branches of the pulmonary arteries. RESULTS: The median diagnostic quality score for both observers was 3.5 (interquartile range 3-4) in the HC group and 2.5 (interquartile range 1.5-3) in the LC group (p<0.01). The median diagnostic confidence score for both observers was 4 (interquartile range 3-4) in the HC group and 3 (interquartile range 1.5-4) in the LC group (p<0.01). Both observers rated examinations as diagnostic in 69% of cases in the LC group, compared with 96% of cases in the HC group. Good interobserver agreement was found in both groups (K value 0.72 in the LC group and 0.73 in the HC). Obesity, poor scan timing, and dilution by venous return of non-opacified blood were the main reasons for a reduction in diagnostic quality of examinations in the LC group. CONCLUSION: Despite a 50% reduction of contrast medium dose in comparison to the standard technique, 150 mg iodine/ml can produce diagnostic MDCT pulmonary angiogram studies in the absence of obesity or high cardiac output and hyper-dynamic pulmonary circulation. Reducing the dose of contrast media would minimize the risk of contrast nephropathy in patients at risk of this complication, particularly those suffering from congestive heart failure in whom intravenous hydration is contraindicated.

Contrast-induced nephropathy: are there differences between low osmolar and iso-osmolar iodinated contrast media?

It is acknowledged that high osmolar contrast media are more nephrotoxic than low (LOCM) or iso-osmolar contrast media (IOCM). However, it remains contentious whether the IOCM are less nephrotoxic in comparison with LOCM. This article reviews published clinical studies that investigated this issue and demonstrates there are no conclusive data to indicate that there is a definite difference in renal tolerance between LOCM and IOCM. All these agents are potentially nephrotoxic in patients with advanced renal impairment. In these patients the smallest possible dose of IOCM or LOCM should be used in addition to adequate hydration to minimize the risk of contrast nephropathy.

Nephrogenic systemic fibrosis: more questions and some answers.

Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder that may develop in patients who have advanced reduction in renal function. A causal relation between gadolinium (Gd(3+))-based contrast agents (Gd-CA) and NSF is probable and is supported by the accumulating data in the literature. From those data, the prevalence of NSF is seen to be significantly higher after exposure to gadodiamide than any other gadolinium-based agent. Gd-CA are either linear or macrocyclic chelates and are available as ionic or non-ionic preparations. The molecular structure, whether cyclic or linear, and the ionicity determine the stability of Gd-CA. Linear chelates are flexible open chains which do not offer a strong binding to Gd(3+). In contrast, the macrocyclic chelates offer a strong binding to Gd(3+) by the virtue of being pre-organised rigid rings of almost optimal size to cage the Gd(3+) atom. Non-ionic preparations are also less stable in comparison to the ionic ones, as the binding between Gd(3+) and the negatively charged carboxyl groups is stronger than that with amides or alcohol in the non-ionic preparations. According to stability constants and kinetic measurements, the most stable Gd-CA is the ionic-macrocyclic chelate Gd-DOTA and the least stable agents are the non-ionic linear chelates gadodiamide and gadoversetamide. The stability of Gd-CA seems to be an important factor in the pathogenesis of NSF. Gd-CA of low stability are likely to undergo transmetallation and release free Gd ions that may deposit in tissues and attract circulating fibrocytes to initiate the process of fibrosis. There have been no cases of NSF reported in the peer-reviewed literature after the exclusive use of the stable macrocyclic Gd-CA. This minireview covers the clinical and pathological features of NSF and updates the current understanding of the pathophysiology of this condition.

Extracellular gadolinium contrast agents: differences in stability.

Extracellular gadolinium contrast agents (Gd-CA) are either linear or macrocyclic chelates available as ionic or non-ionic preparations. The molecular structure whether cyclic or linear and ionicity determines the stability of Gd-CA. Linear chelates are flexible open chains which do not offer a strong binding to Gd(3+). In contrast, the macrocyclic chelates offer a strong binding to Gd(3+) by the virtue of being preorganized rigid rings of almost optimal size to cage the gadolinium atom. Non-ionic preparations are also less stable in comparison to the ionic ones as the binding between Gd(3+) with the negatively charged carboxyl groups is stronger in comparison to that with amides or alcohol in the non-ionic preparations. According to stability constants and kinetic measurements, the most stable Gd-CM is the ionic-macrocyclic chelate Gd-DOTA and the least stable agents are the non-ionic linear chelates gadodiamide and gadoversetamide. In vivo data confirmed the low stability of non-ionic linear chelates but no significant difference was observed amongst the macrocyclic agents whether ionic (Gd-DOTA) or non-ionic such as Gd-HP-DO3A and Gd-BT-DO3A. The stability of Gd-CA seems to be an important factor in the pathogenesis of the serious complication of nephrogenic systemic fibrosis. Gd-CA of low stability are likely to undergo transmetallation and release free Gd ions that deposit in tissue and attract circulating fibrocytes to initiate the process of fibrosis. No cases of NSF have been observed so far after the exclusive use of the stable macrocyclic Gd-CA.

Contrast-induced nephropathy: the wheel has turned 360 degrees.

Contrast-induced nephropathy (CIN) has been a hot topic during the last 5 years due its association with increased morbidity and mortality. CIN is an important complication, particularly in patients with advanced chronic kidney disease (CKD) associated with diabetes mellitus. Methods to diminish the incidence of CIN have been highly contentious. They include choice of contrast, pharmacologic manipulation, and volume expansion. The pathophysiology of this complication remains uncertain, but reduction in renal blood flow and direct toxicity of tubular cells has been implicated. More than 900 publications under the heading CIN have been published during the last 5 years. Fewer than 5% of these publications are randomized prospective controlled studies. In spite of the large number of reports on CIN, very little has been changed. The use of the smallest possible dose of low- or iso-osmolar contrast media, volume expansion, stopping nephrotoxic drugs, and avoiding repeat contrast injections within 48 hours remain the most effective approach to reduce the risk of CIN.

Review article: Acute serious and fatal reactions to contrast media: our current understanding.

Serious or fatal reactions to a contrast medium (CM) are unpredictable but fortunately rare. History of serious reaction to CM, bronchial asthma or multiple allergies increases the incidence of serious reactions by a factor of 5. Serious or fatal reaction to CM could be due to direct effect on basophils and mast cells or IgE mediated (type 1 hypersensitivity reaction). Activation of the kinin system leading to the formation of bradykinin could also be involved. Complement activation is unlikely to be a primary factor in initiating a serious reaction to CM. Avoiding CM administration in patients at high risk of serious reaction is advisable, but if the administration is deemed essential all precautions should be implemented and measures to treat serious reactions should be readily available. Oxygen supplementation, intravenous administration of physiological fluids and intramuscular injection of 0.5 ml adrenalin (1:1000) should be considered in the first line management of acute anaphylaxis. The ability to assess and treat serious CM reaction effectively is an essential skill that the radiologist should have and maintain.

Contrast media-induced nephrotoxicity--questions and answers.

The intravascular administration of contrast media (CM) can produce acute haemodynamic changes in the kidney characterized by an increase in renal vascular resistance and a decrease in the glomerular filtration rate (GFR). These changes may lead to clinically significant reduction in renal function in patients with pre-existing risk factors such as diabetic nephropathy, congestive heart failure and dehydration. The pathophysiology of the renal haemodynamic effects of CM involves activation of the tubuloglomerular feedback (TGF) mechanism and the modulation of the intrarenal production of vasoactive mediators such as prostaglandins, nitric oxide, endothelin and adenosine. The TGF response is osmolality-dependent and accounts for about 50% of the acute functional effects of high osmolar CM on the kidney. Reduction in the synthesis of the endogenous vasodilators nitric oxide and prostaglandins increases the nephrotoxicity of CM. Endothelin and adenosine play a crucial role in mediating the acute functional effects of CM. Antagonists of these mediators attenuate the reduction in renal function induced by contrast agents. Vacuolization of the cells of the proximal tubules and necrosis of those of the medullary ascending limbs of loops of Henle are the main structural effects of CM in the kidney. The reduction in renal function induced by CM could be minimized by the use of low osmolar CM and adequate hydration. The prophylactic administration of calcium channel blockers and adenosine antagonists such as theophylline may also offer some protective effect.

Review article: Effects of radiographic contrast media on the lung.

The pulmonary adverse effects of intravascular use of water soluble radiographic contrast media (RCM) include bronchospasm, pulmonary oedema and increase in the pulmonary arterial blood pressure (Ppa). Symptomatic bronchospasm is rare but subclinical increase in airways resistance is common after intravascular injection of RCM. Experimental studies have demonstrated that the low osmolar ionic dimer ioxaglate can induce significant bronchospasm in comparison with other types of RCM. Histamine and endothelin, which are potent bronchoconstrictors and released in response to the administration of RCM, do not seem to mediate the bronchospastic effect of RCM. Pretreatment with corticosteroids or antihistamine does not appear to prevent RCM induced bronchospasm, but the administration of beta(2) adrenergic agonist can abolish this adverse effect. RCM induced pulmonary oedema can be secondary to endothelial injury causing an increase in the permeability of the microcirculation. It may also occur in patients with incipient cardiac failure, when large doses of RCM particularly of the high osmolar type are used. A rise in Ppa induced by RCM seems to be secondary to an increase in pulmonary vascular resistance through direct effects on the pulmonary circulation. Low osmolar non ionic monomers induce the least changes in the pulmonary circulation and should be the contrast media of choice for intravascular use in patients with pulmonary hypertension. The mechanisms responsible for the effects of RCM on airway resistance and pulmonary circulation remain unclear. Intrabronchial administration of high osmolar water soluble RCM is dangerous and can induce severe bronchial irritation and pulmonary oedema. Low osmolar RCM are well tolerated by the lungs following aspiration with minimal histological reaction.

High resolution volume imaging of airways and lung parenchyma with multislice CT.

The value of multislice CT (MSCT) in imaging the peripheral airways and lung parenchyma has not been widely investigated. In this article the authors' experience in the use of MSCT (4-slice scanner) in imaging patients with suspected parenchymal lung disease or airways abnormalities will be presented. The technique described should be modified with the more modern 8-slice or 16-slice scanners. The whole thorax is scanned contiguously using 4 x 1 mm collimation from the lung bases up to apices in end-inspiration while the patient is in the prone position. Collimation of 2 x 0.5 mm is used at 8-10 levels evenly spaced in expiratory scans and also in the breathless patient who is scanned during gentle breathing. High resolution images of the lungs (1 mm slice thickness) are reconstructed in the following planes: axial (10 mm apart from apices to bases), coronal (six evenly spaced through the chest) and sagittal (four images evenly spaced through each lung). Paddlewheel reconstruction is used if further assessment of the airways is required, and three-dimensional imaging is used mainly for assessment of the trachea and major bronchi. Contiguous axial images (10 mm slice thickness) of the whole lung and mediastinum are also produced and referred to as a screenogram. Axial images of 1 mm slice thickness are produced with expiratory scans and for breathless patients. All the images are produced independently by the radiographic staff and are provided as hard copies (20 frames/film) for reporting. However, if facilities are adequate, direct reporting from the workstation is more effective in reviewing large number of images. The technique is effective in assessment of infiltrative lung disease, emphysema, bronchiectasis and central airways. The screenogram offers comprehensive evaluation of the lung and mediastinum, but the radiation dose associated with high resolution volume imaging remains a source of concern.

Endothelin: what does the radiologist need to know?

Endothelin (ET) is a potent endogenous vasoconstrictor peptide. It has been implicated in various pathological states since its discovery in 1988. The cardiovascular system and the kidneys are important sites for the action of this peptide. Two types of ET receptor, ETA and ETB, govern the biological effects of ET. Drugs that can prevent the endogenous synthesis of ET or block its binding to receptors may offer important therapeutic impact to patients with congestive heart failure, pulmonary hypertension and acute renal failure. Areas of particular interest to the radiologist include the role of ET in mediating some of the side effects of contrast media, particularly contrast medium nephropathy, and the involvement of ET in the pathogenesis of restenosis following angioplasty. This review outlines the basic biology of this important mediator and its role in health and disease.

Effect of radiographic contrast media on histamine release from human mast cells and basophils.

Radiographic contrast media (RCM) cause histamine-dependent allergic-like reactions. The direct effects of diatrizoate (high osmolar ionic monomer), ioxaglate (low osmolar ionic dimer), iopromide (low osmolar non ionic monomer) and iotrolan (iso-osmolar non ionic dimer) at the concentration of 200 mgI ml-1 (60 min exposure) on the release of histamine from human basophils, human lung mast cells (HLMC), and human skin mast cells (HSMC) were investigated. Diatrizoate induced 48 +/- 4% histamine release in basophils, 15 +/- 3% in HLMC and 25 +/- 6% in HSMC. The remaining RCM were relatively ineffective activators of histamine release in both HLMC and HSMC (ioxaglate 4 +/- 1% and 4 +/- 1%, iopromide 5 +/- 1% and 7 +/- 2%, iotrolan 7 +/- 2% and 10 +/- 3%, respectively). Both iotrolan and ioxaglate were effective in basophils inducing 21 +/- 3% and 24 +/- 6% histamine release, respectively, whereas iopromide was relatively ineffective (7 +/- 4%). Diatrizoate induced histamine release from all three cell types with optimal levels of histamine release after a 2-4 h incubation although significant levels occurred within 15 min. Dose-dependent histamine release from HLMC occurred in all four types of RCM, the largest response (37 +/- 3%) being produced by diatrizoate. The effect of osmolality on histamine release was investigated using different concentrations of mannitol solutions (0.25, 0.5 and 1 M). Histamine release from HLMC, HSMC and basophils after 90 min exposure to mannitol (1 M) was 24 +/- 2% (p < 0.05), 9 +/- 3% (p = 0.06) and 49 +/- 1% (p < 0.05), respectively, suggesting that hyperosmolality per se can induce histamine release from basophils and mast cells. Diatrizoate-induced histamine release in all three cell types was significantly reduced by lowering the temperature to 0 degree C and partially attenuated by the metabolic inhibitors antimycin A (1 microM) and 2-deoxyglucose (5 mM), and by the omission of glucose from the buffer solution. Diatrizoate-induced histamine release was not dependent on extracellular calcium. These data suggest that diatrizoate induces histamine release at least in part by non-cytotoxic mechanisms.

Contrast media and the kidney: European Society of Urogenital Radiology (ESUR) guidelines.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) has looked at the effects of contrast media on the kidney including prevention of contrast medium induced nephropathy. This has resulted in four reports dealing with 1) contrast medium induced nephrotoxicity, 2) haemodialysis and contrast media, 3) use of gadolinium contrast media instead of iodinated contrast media and 4) contrast media injection in diabetic patients receiving metformin. The review presents an overview of these four reports and offers the current understanding of the interaction between contrast agents and the kidney.

Effect of radiographic contrast media on endothelium derived nitric oxide-dependent renal vasodilatation.

The effect of diatrizoate (Urografin325) on the cumulative dose-response curve of the vasodilatory response to acetylcholine was studied in the isolated perfused rat kidney (IPRK). The effect of 1-nitroarginine methyl ester (L-NAME) (10 mumol l-1) on the cumulative concentration-response curve of the vasodilatory response to acetylcholine and sodium nitroprusside was also studied. Acetylcholine is a vasodilator dependent on nitric oxide (NO) synthesis by the endothelium; sodium nitroprusside is a vasodilator not dependent on endogenous NO synthesis and L-NAME is an inhibitor of endogenous NO synthesis. The effect of L-NAME (10 mumol l-1) on the vasodilatory effect of diatrizoate which is observed in the presence of endothelin A receptor antagonist (BQ123, 10 mumol l-1) was also studied. In all experiments an infusion of angiotensin II (5 ng min-1) was maintained to increase the vascular tone of the preparation. Acetylcholine induced vasodilatation and the maximum increase in renal perfusate flow (RPF) was 17.0 +/- 1.7%, (p < 0.05). Diatrizoate (20 mgl ml-1 perfusate concentration) which induced a sustained fall in the RPF (-31.0 +/- 1.7%, p < 0.05) had no effect on the vasodilatory response to acetylcholine, and a similar increase in the RPF (17.8 +/- 2.2%, p < 0.05) was observed. In contrast, L-NAME (10 mumol l-1) completely abolished the vasodilatory effect of acetylcholine and produced instead a modest decrease in RPF by -5.0 +/- 1.7% (p < 0.05). The vasodilatory effect of sodium nitroprusside was not affected by L-NAME, confirming its selectivity as an inhibitor of endogenous NO synthesis in the IPRK. The maximum increase in the RPF induced by sodium nitroprusside was 23.1 +/- 2.0% (p < 0.05) in the absence of L-NAME and 21.2 +/- 2.2% (p < 0.05) in its presence. L-NAME did not interfere with the vasodilatation induced by diatrizoate in the presence of BQ123. In the presence of BQ123 alone the RPF increased from 23.3 +/- 1.4 ml min-1 g-1 to 26.5 +/- 1.0 ml min-1 g-1 (p < 0.05). In the presence of L-NAME and BQ123 the RPF increased from 24.4 +/- 3.0 ml min-1 g-1 to 27.2 +/- 2.7 ml min-1 g-1 (p < 0.05). There was no difference between the two groups (p > 0.05). In conclusion, diatrizoate did not interfere with endothelium derived NO-dependent vasodilatation in the kidney. A reduced production of NO in the vascular endothelium induced by contrast media is unlikely to play any role in the pathophysiology of the increase in renal vascular resistance produced by these agents. The renal vasodilatation induced by diatrizoate is not dependent on endogenous production of NO.

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.

Effects of radiographic contrast media on pulmonary vascular resistance of normoxic and chronically hypoxic pulmonary hypertensive rats.

Intravascular radiographic contrast media (RCM) can be associated with significant morbidity in patients with pulmonary hypertension (PH). This study investigated the direct effect of the four main classes of RCM (high osmolar ionic monomer "diatrizoate"; low osmolar ionic dimer "ioxaglate"; low osmolar non-ionic monomer "iopromide"; and iso-osmolar non-ionic dimer "iotrolan") in ex vivo isolated rat lungs perfused with blood at 20 ml min(-1) under basal conditions (air + 5% CO2 ventilation, pulmonary artery pressure (Ppa) 16-20 mmHg) and when Ppa was raised by hypoxic vasoconstriction in normal rats (2-3% O2+5% CO2 ventilation, Ppa increased by 4-14 mmHg). The effects of low osmolar RCM (ioxaglate, iopromide and iotrolan) were also studied in rats with PH induced by chronic hypoxia (3 weeks 10% O2, Ppa 26-36 mmHg). Increasing volumes (0.05 ml, 0.1 ml, 0.3 ml, and 0.5 ml) of RCM, mannitol (osmolar and pH control) or normal saline (volume control) were added to the 10 ml blood reservoir (n=4-9 per group). In normal rats, RCM caused a dose-dependent slow rise in Ppa. The maximum rise in mean+/-SEM Ppa at the cumulative dose of 0.95 ml was ioxaglate 13.8+/-1.6 mmHg>iotrolan 7.3+/-1.7 mmHg=diatrizoate 9.8+/-2.2 mmHg>iopromide 3.0+/-0.8 mmHg (p<0.05). The rise in Ppa induced by ioxaglate and iotrolan was significantly greater than in the mannitol and saline controls (p<0.05). Pre-treatment with endothelin receptor A/B blockade (SB209670) did not abolish the rise in Ppa induced by diatrizoate (0.95 ml) in the normal rat (3.8+/-1.3 mmHg diatrizoate alone and 3.4+/-1.1 mmHg in the presence of 40 microM SB209670, n=5 per group). When Ppa was raised by acute hypoxia, ioxaglate and diatrizoate (0.5 ml) caused a fall in Ppa (percentage fall -53+/-23 and -118+/-10, respectively, p<0.001) while iotrolan and iopromide caused a small further rise in Ppa, which was significant with iotrolan at a dose of 0.3 ml (percentage rise in pressure 14.2+/-2.3, p<0.05). In chronic pulmonary hypertensive rats, RCM (0.95 ml) caused an overall slow progressive rise in Ppa (iopromide 6.8+/-1.7 mmHg< ioxaglate 11.6+/-2.5 mmHg=iotrolan 12.7+/-1.1 mmHg). However, ioxaglate initially induced an acute fall of Ppa (maximum fall 4.22+/-0.9 mmHg, p<0.05) for almost 20 min. In summary, iopromide induced the least change in Ppa of normal and pulmonary hypertensive rats. The pathophysiology of the effects of RCM on the pulmonary circulation remains uncertain.

Effects of radiographic contrast media on the tension of isolated small pulmonary arteries.

The aim of the study was to establish the direct effects of radiographic contrast media (RCM) on the tension of isolated small pulmonary arteries and to investigate any mediation by nitric oxide (NO) and endothelin (ET). Small pulmonary arteries (0.3-0.6 mm in diameter) from male Wistar rats were mounted in a Cambustion vessel myograph and vessel wall tension recorded. The effects of 10, 20, 40, 80, 150, 200 and 250 mgl mI-1 of diatrizoate, ioxaglate, iopromide and iotrolan and their mannitol osmolar control from basal condition, and when the vessels were preconstricted with prostaglandin F2 alpha (PGF2 alpha) either submaximally (10 microM) or maximally (100 microM), were studied. The constrictor response to diatrizoate (40 mgI ml-1) was tested in the presence of non-selective endothelin receptor antagonist (10 microM SB209670). The dilator response to ioxaglate (80 mgI ml-1) was tested in the presence of L-nitroarginine methyl ester (L-NAME, 100 microM). All RCM caused biphasic changes in tension, a small transient fall (dilatation) followed by a sustained rise (constriction). Mannitol caused constriction only. The potency order of constrictions at 10-40 mgI ml-1 was diatrizoate > iopromide > ioxaglate > iotrolan. When the vessels were preconstricted with PGF2 alpha, RCM caused predominantly dilatation; ioxaglate produced the largest effect (-42.1 +/- 3.1%, n = 12). Mannitol caused constriction only. SB209607 had no effect on the constrictor effect of diatrizoate [41.9 +/- 2.3 alone, 42.1 +/- 2.7 with SB209670, n = 10]. L-NAME had no effect on the dilator response to ioxaglate [-38.2 +/- 1.6 alone, -43.6 +/- 2.2 with L-NAME, n = 8]. It is tempting to postulate that dimeric RCM may cause the least changes in the pulmonary circulation during angiography.

Clinicians' interpretation of the indeterminate ventilation-perfusion scan report.

Most patients with suspected pulmonary embolism are initially investigated by radio-nuclide ventilation-perfusion (VQ) scanning. Approximately 70% of VQ scans are "indeterminate". Further investigations should be considered in such patients in order to establish a definitive diagnosis. However, these investigations are rarely requested in patients with indeterminate scans in our institution. We therefore decided to review the casenotes of such patients to determine their subsequent management. Over a 9 month period, 131 (32%) out of a total of 413 consecutive VQ scans were reported as indeterminate. The casenotes of 111 of these patients (65 female, 46 male, mean age 65 years, range 17-91 years) were reviewed. 52 of the 111 patients (46%) were treated on clinical grounds without further investigation; 12 patients (11%) had further investigation; and in 39 of the cases (35%) the VQ scan report was misinterpreted. 20 (38%) of the 52 patients managed on clinical grounds were treated for pulmonary embolus with anticoagulation and 26 (50%) were not anticoagulated. Of the 12 patients who were investigated further, nine had lower limb Doppler ultrasound and three had contrast venography. No patients had pulmonary angiography. Of the 39 cases where the VQ report was misinterpreted, the result was misquoted in the casenotes of 37 (95%) as negative for PE and none of these patients were anticoagulated, and in two cases (5%) it was misquoted as positive for PE and anticoagulant therapy was instituted. The misunderstanding was observed in all clinical firms. Such misinterpretation may have significant implications, since 30-40% of patients with indeterminate scans may have had PE. Our findings suggest that clinicians need to be better informed of the significance of an indeterminate VQ scan result.

Multislice helical CT: the value of multiplanar image reconstruction in assessment of the bronchi and small airways disease.

We examined 23 consecutive patients (11 males and 12 females with mean age of 56 years) with possible airway diseases to assess the impact of multiplanar image reconstruction (MPR) on the degree of confidence and accuracy in diagnosing bronchial abnormalities and emphysema. The thorax was scanned contiguously at 1 mm slice thickness using Siemens Volume Zoom Multislice CT scanner. Images were reconstructed at 1 mm slice thickness (lung windows L-600HU W-1600HU utilizing high spatial frequency algorithm) in the axial (10 mm apart), sagittal (4 images per lung) and coronal (6 images) plane. Paddle wheel image reconstructions were also performed in the assessment of bronchiectasis. Axial images were assessed with and without the help of MPR by three chest radiologists at two separate occasions (at least 4 weeks apart). The presence of bronchiectasis, emphysema and bronchiolitis in each lobe was documented on a confidence scale of 0 to 3. The overall mean confidence for each observer with and without MPR was compared. Consensus diagnosis was used as the gold standard for the assessment of the diagnostic accuracy of each observer. A confidence score of 2 or more for any lobe was considered diagnostic of the particular airway disease. The diagnostic accuracy for each observer with and without MPR was compared. Consensus reporting diagnosed bronchiectasis in 7 patients (30.4%), bronchiolitis in 5 patients (21.7%) and emphysema in 12 patients (52%). MPR did not increase the confidence of assessing the different abnormalities for all observers but improvement in diagnosing bronchiectasis was noted in two observers. The improvement did not reach statistical significance. However, agreement between observers in the diagnosis of bronchiectasis and emphysema was improved when the MPR images were used in conjunction with standard axial imaging (Kappa statistic improved from 0.29 to 0.54 for bronchiectasis and from 0.7 to 0.81 for emphysema). Agreement on the diagnosis of bronchiolitis was not improved by MPR for all observers. Our results suggest that MPR seems to improve the confidence in diagnosing bronchiectasis and emphysema.

Ventilatory effects of radiographic contrast media.

Respiratory adverse reactions have been reported with the use of contrast media. This study investigates the effects of different radiographic contrast media (RCM) on ventilation and blood gases. Tidal volume and respiratory rate of male Wistar rats anaesthetised with Inactin (100 mg kg-1 intraperitoneally), were measured continuously by integration of tracheal airflow. Contrast media (diatrizoate 370, ioxaglate 320 and iopromide 300) or mannitol controls matched for volume, pH and osmolarity (4 ml kg-1) were administered via a jugular cannula (n > or = 6 per group). Carotid artery blood was sampled at 2, 7, 12, 17, 25 and 30 min post-injection for PaO2, PaCO2 and pH. Systemic blood pressure was monitored from the same cannula. No significant reduction was observed in minute ventilation (tidal volume x respiratory rate per minute) with any of the contrast media. All contrast media and control solutions produced a fall in PaO2 within 4 min; returning to basal levels at 10 min (diatrizoate 35.6% (p < 0.05), ioxaglate 15.2% (p < 0.02), iopromide 16.2% (p < 0.01); controls: 17.3% (p < 0.01), 13.5% (p < 0.02) and 12.0% (NS), respectively). The fall in PaO2 induced by diatrizoate was significantly (p < 0.05) larger in comparison to the other groups. Ioxaglate, iopromide and their mannitol controls induced a comparable fall in PaO2. There was a concurrent rise in PaCO2 and fall in pH that reached significance for diatrizoate (p < 0.01). The changes in blood gases with RCM administration cannot be explained by changes in ventilation and may be due to an effect on pulmonary perfusion.

Effect of diatrizoate on the function of the isolated perfused rat kidney.

The mechanism of the nephrotoxicity of water-soluble contrast media (WSCM) remains ill defined. We have studied the effect of diatrizoate on the isolated perfused rat kidney (IPRK). Emphasis was on the effect of low- and high-dose diatrizoate on glomerular filtration rate (GFR), renal perfusate flow (RPF), fractional excretion of albumin (FE Alb) and fractional reabsorption of sodium (FR Na). The addition of diatrizoate to the IPRK led to a dose-dependent biphasic change in RPF and GFR characterized by an initial transient increase followed by a marked and sustained decrease. Diatrizoate induced a diuresis and a parallel increase in urinary sodium excretion (fall of FR Na). Fe Alb was also increased in kidneys exposed to diatrizoate. Electron microscopy of a control kidney showed preservation of cellular architecture, which contrasted with the observed cytoplasmic vacuolation of proximal tubular cells after perfusion with diatrizoate. This study confirms a direct effect of WSCM on the function of the IPRK. In this experimental model, diatrizoate reproduces the effects observed in vivo on GFR and renal perfusion.