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S K Morcos

Publications and source records attributed to S K Morcos.

At least 37 records · Page 2Linked to original sources
PubMed2001

Radiographic contrast media induced nephropathy: experimental observations and the protective effect of calcium channel blockers.

Combined acute inhibition of the synthesis of nitric oxide with L-nitroarginine methyl ester (L-NAME) and of prostacycline synthesis with indomethacin predisposes rats to severe renal injury from radiographic contrast media. The reliability of this pharmacological manipulation in the study of radiographic contrast medium induced nephropathy (RCMN) was investigated. Adult male Sprague-Dawley rats were injected with iv L-NAME (10 mg kg(-1)) and iv indomethacin (10 mg kg(-1)) 15 min apart and prior to injection of RCM or normal saline (control group). A dose-dependent reduction in renal function was observed after intravascular injection of the high osmolar RCM diatrizoate (Angiografin, 306 mgI ml(-1)). A significant (p<0.01) increase in serum creatinine (Cr) (from 54.66+/-8.39 micromol l(-1) to 171.96+/-24.49 micromol l(-1) and from 80.95+/-6.73 micromol l(-1) to 204.76+/-16.73 micromol (-1), n=5 per group) was observed 24 h after injection of 6 ml and 8 ml of diatrizoate, respectively. The increase in serum Cr after injection of 8 ml of diatrizoate recovered spontaneously to 80.87+/-8.70 micromol l(-1) 7 days after injection. No significant change in renal function was observed in the control group (n=5) receiving 8 ml kg(-1) of normal saline or after injection of 4 ml of diatrizoate (serum Cr 69.84+/-5.5 micromol l(-1) pre contrast injection and 66.67+/-13.47 micromol l(-1) 24 h post contrast injection, n=5). The increase in serum Cr observed with 6 ml of diatrizoate was significantly higher (p<0.01) than the rise induced by equivolume of the low osmolar non-ionic monomer iopromide (Ultravist, 300 mgI ml(-1)) (serum CR 68.47+/-8.39 micromol l(-1) pre contrast injection and 143.59+/-32.03 micromol l(-1) 24 h post contrast injection, n=5). The calcium channel blocker diltiazem (10 mg kg(-1) injected intraperitoneally 30 min prior to RCM injection) prevented the rise in serum Cr observed with 6 ml of diatrizoate (serum Cr pre contrast injection 70.31+/-7.28 micromol(-1) and 78.21+/-17.81 micromol(-1) 24 h post contrast injection in animals pre-treated with diltiazem, n=5). The protective effect against RCM-induced reduction in renal function was less with lower doses of diltiazem. In conclusion, the animal model used is reliable and reproduced previously established observations in the field of RCMN. The protective effect of a calcium channel blocker at the appropriate dose against RCMN has also been shown. The clinical effectiveness of this class of drugs in preventing RCMN requires further evaluation.

Animals↗
PubMed2001

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.

Analysis of Variance↗
PubMed2000

Effects of radiographic contrast media on proliferation and apoptosis of human vascular endothelial cells.

The aim of the study was to determine the effects of radiographic contrast media (RCM) on proliferation and apoptosis of human vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were exposed for either 1 min or 15 min to RCM (diatrizoate, ioxaglate, iopromide, iotrolan) at an iodine concentration of 250 mgl ml-1. Controls were complete growth medium (CGM) and saturated mannitol (osmotic control). [3H]thymidine incorporation was used to determine cell proliferation 24 h after exposure. Apoptosis was determined at 1 h and 6 h by terminal uridine nick end labelling (TUNEL), time lapse video microscopy (TLVM) and DNA electrophoresis. Mean proliferation rates (%) (+/- SEM) (p-values compared with the CGM control) at 1 min and 15 min, respectively, were: diatrizoate: 31.9 (10.6), 5.8 (1.5) (p < 0.001); ioxaglate: 48.4 (10.9), 20.4 (4.5) (p < 0.001); iopromide: 63.4 (8.7), 58.2 (10.2) (p < 0.05); iotrolan: 84.7 (7.3), 72.8 (12.4) (p = ns); saturated mannitol 50.5 (9.6), 45.9 (10.0) (p < 0.001). Mean apoptotic indices (%) (+/- SEM) at 1 h and 6 h following 1 min exposure, respectively, were: CGM: 0.25 (0.13), 0.23 (0.08); diatrizoate: 2.18 (0.19), 2.69 (0.34) (p < 0.001); ioxaglate: 1.90 (0.23), 1.69 (0.02) (p < 0.05); iopromide: 0.59 (0.04), 0.33 (0.02) (p = ns); iotrolan: 0.30 (0.07), 0.27 (0.1) (p = ns); saturated mannitol 2.11 (0.24), 1.4 (0.1) (p < 0.05). After 15 min exposure, apoptosis rates at both 1 h and 6 h, respectively, were: iotrolan: 0.29 (0.17), 0.51 (0.16) (p = ns); diatrizoate: 3.19 (0.81), 11.66 (1.75) (p < 0.001); ioxaglate: 1.88 (0.14), 2.87 (0.20) (p < 0.05); iopromide: 1.06 (0.11), 1.52 (0.15) (p < 0.05); saturated mannitol 1.62 (0.09), 4.63 (0.74) (p < 0.05). TLVM and DNA electrophoresis confirmed the occurence of apoptosis after exposure to RCM. In conclusion, saturated mannitol and all tested RCM, with the exception of iotrolan, (diatrizoate > ioxaglate > iopromide) reduced proliferation and increased apoptosis of HUVECs. The effects were more pronounced with ionic RCM and seem to depend on osmolality as well as the chemical structure of these agents. Endothelial injury and apoptosis may be responsible for some of the side effects associated with intravascular use of RCM.

Apoptosis↗
PubMed2000

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.

Angioplasty, Balloon↗
PubMed2000

Effects of adenosine receptor antagonists on the responses to contrast media in the isolated rat kidney.

Contrast media can induce both a decrease in renal blood flow and a reduction in glomerular filtration rate (GFR) when administered to both experimental animals and humans. In the present study we have examined the role of adenosine in mediating these effects using the isolated perfused rat kidney. Kidneys were perfused with a 6. 7%-(w/v)-albumin-based perfusate supplemented with glucose and amino acids (n=6 per group). They were exposed to diatrizoate [20 mg of iodine (mgI)/ml; osmolality 1650 mOsm/kg of water] or iotrolan (20 mgI/ml; osmolality 320 mOsm/kg of water) in the presence or absence of theophylline (10.8 microg/ml), or to diatrizoate in the presence or absence of a specific adenosine A(1) receptor antagonist (KW-3902; 2 microg/ml) or a specific A(2) receptor antagonist (KF17837; 6 microg/ml). Diatrizoate (n=6) produced a fall in GFR from 0.65+/-0.04 to 0.42+/-0.03 ml.min(-1).g(-1) (P<0.05); renal perfusate flow (RPF) also declined, from 36.5+/-3.8 to 22.0+/-3.2 ml. min(-1).g(-1) (P<0.05). Iotrolan (n=6) produced a fall in GFR from 0. 64+/-0.02 to 0.48+/-0.04 ml.min(-1).g(-1) (P<0.05) and in RPF from 33.3+/-3.8 to 24.0+/-3.0 ml.min(-1).g(-1) (P<0.05). Theophylline (10.8 microg/ml) prevented the fall in GFR caused by either diatrizoate (baseline, 0.63+/-0.05 ml.min(-1).g(-1); diatrizoate+theophylline, 0. 60+/-0.04 ml.min(-1).g(-1)) or iotrolan (baseline, 0.64+/-0.04 ml. min(-1).g(-1); iotrolan+theophylline, 0.67+/-0.05 ml.min(-1).g(-1)), but did not affect the decreases in RPF caused by either agent. KW-3902 (2 microg/ml) also prevented the fall in GFR produced by diatrizoate (baseline, 0.66+/-0.05 ml.min(-1).g(-1); diatrizoate+KW-3902, 0.61+/-0.05 ml.min(-1).g(-1)), while the fall in RPF remained unaffected. KF17837 (6 microg/ml) had no effect on the decreases in either GFR or RPF induced by diatrizoate (n=6 per group). The results suggest a role for adenosine acting at the A(1) receptor in mediating the decrease in GFR induced by contrast media. This effect is independent of a change in renal vascular resistance, and possibly secondary to mesangial cell contraction causing a decrease in the ultrafiltration coefficient.

Adenosine↗
PubMed1999

Contrast media and metformin: guidelines to diminish the risk of lactic acidosis in non-insulin-dependent diabetics after administration of contrast media. ESUR Contrast Media Safety Committee.

The purpose of this study was to establish guidelines on how to avoid metformin-induced lactic acidosis following intravascular use of contrast media. We reviewed articles published in international journals. No conclusive evidence was found to indicate that the intravascular use of contrast media precipitated the development of metformin-induced lactic acidosis in patients with normal S-creatinine (< 130 mumol/l). The complication was almost always observed in non-insulin-dependent diabetic patients with decreased renal function before injection of contrast media. Guidelines for the use of contrast media in this group of patients are proposed.

Acidosis, Lactic↗
PubMed1999

Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR).

The purpose of this study was, using consensus methodology, to document current understanding of contrast media nephrotoxicity (CMN) and to identify areas where there is disagreement or confusion. To draw up guidelines for avoiding CMN based on the current understanding of the condition established by the survey. One hundred sixty-four statements were mailed to 148 members of the European Society of Urogenital Radiology (ESUR) and to 48 experts in the field of CMN. They were asked about the definition, clinical features, predisposing factors and pathophysiology of CMN and about prophylactic measures. The importance of the statements was rated on a scale from 1 to 10 (1 least important, 10 most important). Fifty-three members (38%) and 23 experts (48%) responded. Both groups considered that an increase in serum creatinine that peaks within 3-4 days and a decrease in creatinine clearance are the most important (rating > 7) features of CMN. Enzymuria was not considered important (rating < 6). Pre-existing renal insufficiency, diabetic nephropathy, dehydration, congestive heart failure, concurrent administration of nephrotoxic drugs and the dose and type of contrast media were considered to be risk factors. Reduction in renal perfusion and damage to tubular cells were considered the main factors in the pathophysiology of CMN (rating > 6). Hydration and the use of low osmolar contrast media were thought to minimize the incidence of CMN (rating > 6). The majority of the responders (84.6% of members and 95.5% of experts) believe that the incidence of CMN in patients with normal renal function is less than 5%. Of the members, 62.5%, and 35.3% of experts, believe that the incidence of CMN is 20-30% in the presence of risk factors. There was disagreement about the definition of CMN, the threshold dose of contrast media above which renal complications may develop, the safe period between repeat injections, the relevance of contrast media renal retention shown on CT and whether contrast media have long-term effects on renal function. The survey showed good understanding of CMN among those who answered the questionnaires, although areas of disagreement remain which require further research. Simple guidelines are proposed.

Contrast Media↗
PubMed1999

Congenital bronchial atresia--presentation of three cases and a pictorial review.

Congenital bronchial atresia (CBA) is a rare anomaly that results from a congenital focal obliteration of a proximal segmental or subsegmental bronchus with the normal development of distal structures. The short atretic segment leads to accumulation of mucus within the distal bronchi to form a bronchocoele and underventilation of the affected part of the lung. The clinical and radiographic features of three cases of CBA are reported and the literature is reviewed. Radiologically, CBA is characterized by the presence of a branching opacity, the bronchocoele, radiating from the hilum surrounded by an area of hyperlucency. These features can be recognized on the chest radiograph but are more clearly defined by computed tomography. Fibreoptic bronchoscopy (FOB) is often required to exclude acquired proximal bronchial obstruction by tumour, foreign body or inflammatory stricture. In CBA a blind-ending bronchus may be revealed, although FOB is often normal. Bronchographic examination is generally abnormal but the appearances may be confusing and is rarely performed. Pathologically, CBA is characterized by a blind-ending bronchus associated with dilated distal bronchi containing impacted mucus. The surrounding lung parenchyma is hyperinflated due to collateral air drift. CBA can be identified accurately by imaging techniques which may make surgery unnecessary in asymptomatic cases.

Adolescent↗
PubMed1999

The effect of antihistamine, endothelin antagonist and corticosteroid prophylaxis on contrast media induced bronchospasm.

Bronchospasm is a well recognized adverse reaction to radiographic contrast media (RCM) and may occur more frequently in asthmatics and atopics. This study was designed to identify RCM which are most likely to cause bronchospasm and to investigate underlying mechanisms mediating this response. Guinea pigs (mean body weight 550 g, n = 46) were anaesthetized with Hypnorm (5 ml kg-1) and Hypnovel (2 ml kg-1) and tracheal, jugular and pleural cannulae introduced. Total airways resistance (Raw) was calculated from the slope of the pressure/flow relationship. The effects of RCM (diatrizoate 370 mgI ml-1, ioxaglate 320 mgI ml-1, iotrolan 300 mgI ml-1 and iopromide 300 mgI ml-1) at a dose of 4 ml kg-1 body weight or control solutions matched for volume, pH and osmolarity administered via the jugular vein on Raw were studied. The effects of pre-treatment (30 min before the administration of RCM) with antihistamine (Mepyramine (30 mg kg-1 i.p.)) or non-selective endothelin receptor antagonist (SB209670 (1 mg kg-1 i.v.)) were investigated. The effectiveness of corticosteroids prophylaxis (prednisolone (20 mg kg-1 i.p.)) administered 18-24 h and 1 h pre-RCM was also assessed. Control animals received normal saline pre-treatment before RCM administration. Lungs were taken for histological examination 30-40 min post-administration of RCM. Only ioxaglate caused a significant (p < 0.05) increase in Raw (5.19 +/- 0.58 to 13.95 +/- 3.53 mmHg ml-1 min-1). Neither mannitol nor saline control solutions had any effect on Raw. Pre-treatment with Mepyramine, SB209670 or prednisolone caused no significant change in the ioxaglate induced increase in Raw. Histological examination of lung tissue from ioxaglate treated animals showed no important abnormalities. In summary, only the ionic dimer ioxaglate caused an increase in Raw. This effect was independent of osmolarity and could be the result of the chemical composition of the contrast agent. It was not an inflammatory response and could not be prevented by prophylactic treatment with antihistamine, endothelin antagonist or corticosteroids. The mechanisms responsible for the increase in Raw remain uncertain.

Airway Resistance↗
PubMed1998

The haemodynamic effects of iodinated water soluble radiographic contrast media: a review.

All classes of iodinated water-soluble radiographic contrast media (RCM) are vasoactive with the iso-osmolar dimers inducing the least changes in the vascular tone. The mechanisms responsible for RCM-induced changes in the vascular tone are not fully understood and could be multifactorial. A direct effect on the vascular smooth muscle cells causing alterations in the ion exchanges across the cell membrane is thought to be an important factor in RCM-induced vasodilatation. The release of the endogenous vasoactive mediators adenosine and endothelin may also play a crucial role in the haemodynamic effects of RCM particularly in the kidney. In addition, the effects of RCM on blood rheology can cause a reduction in the blood flow in the microcirculation. The purpose of this review is to discuss the pathophysiology of the haemodynamic effects of RCM and to offer some insight into the biology of the endothelium and vascular smooth muscle cells as well as the pharmacology of the important vasoactive mediators endothelin and adenosine.

Adenosine↗