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PubMed1999

Aquaporin-1 expression in proximal tubule epithelial cells of human kidney is regulated by hyperosmolarity and contrast agents.

Primary cells of renal proximal tubule epithelium (S1 segment) of human kidney (HRPTE cells) up-regulate aquaporin-1 (AQP-1) expression in response to hyperosmolarity. NaCl and D(+)-raffinose increased (2-2.5 fold) AQP-1 expression when medium osmolarity was 400 and 500 mOsm/kg.H2O. Urea did not have this effect. Unlike our previous findings with mIMCD-3 cells, vasopressin (10(-8)M) did not affect AQP-1 expression in HRPTE cells in isosmolar or NaCl-enriched hyperosmolar conditions. Furthermore, HRPTE cells increased (3-4 fold) AQP-1 expression when exposed to hyperosmolar Reno-60 and Hypaque-76 (diatrizoates, ionic) contrast agents at 400 and 500 mOsm/kg.H2O. Isosmolar (290 mOsm/kg H2O) Visipaque (iodixanol, non-ionic) at 10% (v/v) concentrations also increased AQP-1 expression, and 25% v/v of Visipaque rendered morphological alterations of HRPTE cells and a 3-fold increase in AQP-1 expression after 24h exposure. Finally, semi-quantitative RT-PCR of HRPTE cells subjected to various isosmolar or hyperosmolar conditions demonstrated up-regulation of AQP-1 mRNA and protein levels. Our results suggest AQP-1 up-regulation in HRPTE cells exposed to environmental stresses such as hyperosmolarity and high doses of isosmolar contrast agents.

Aquaporins↗
PubMed1997

The role of endothelin in radiocontrast nephropathy.

In the present study we investigated the role of endothelin and AT II in radiocontrast nephropathy induced in rats with reduced renal mass (70-75%). Thirty-five male Wistar albino rats weighing between 280 and 400 g were anaesthetized with ketamine (130 mg/kg b.w.) and right total, left 50% nephrectomy were performed. After this operation, the rats were kept under observation for six to eight weeks and then they were randomly separated into three groups. Group I rats were infused with 8.9 ml/kg (or 2.9 g of iodine/kg body weight) Na diatrizoate (Urovision, 1,500 mosm/kg). Group II rats were infused with 0.9% NaCl in an equal volume with the radiocontrast material. Group III rats were given 4.5% NaCl that had the same volume and osmolality as the radiocontrast material. Two hours after the drug infusions, blood and accumulated urine samples were collected from all the rats and tested for endothelin, AT II, BUN, creatinine, uric acid, electrolytes, calcium and phosphorus. We found that the plasma endothelin levels in Group I (77.64 +/- 29.62 pg/ml) were significantly higher than in Group II (20.52 +/- 5.83 pg/ml) and Group III (15.04 +/- 5.15 pg/ml) (t = 8.34 and t = 9.14, respectively, p < 0.001). Therefore elevation in circulating endothelin might have been an additional factor leading to the radiocontrast-induced nephrotoxicity.

Angiotensin II↗
PubMed1985

Absence of myocardial biochemical toxicity with a nonionic contrast agent (iopamidol).

To evaluate the myocardial metabolic effects of a new nonionic contrast agent, iopamidol, a randomized, double-blind study was performed comparing iopamidol with sodium meglumine diatrizoate (Renografin-76) in 23 patients with ischemic heart disease. Coronary sinus and arterial metabolic samples were obtained prior to and during the 20-minute period following the contrast left ventriculogram. Ten patients received iopamidol and 13 received Renografin-76. The chemical lactate extraction in the iopamidol group was 13 +/- 9% prior to left ventriculography and 17 +/- 12% following the contrast injection (p less than 0.005). In the Renografin-76 group, the lactate extraction was 23 +/- 13% and decreased significantly to 12 +/- 24% following the ventriculogram (p less than 0.01). In a subset of these patients (n = 10), [1-(14)C] lactate was infused as a tracer to quantitate the amount of lactate released by the myocardium. [1-(14)C] lactate analysis demonstrated that the fall in lactate extraction ratio following Renografin-76 was due to an increase in myocardial lactate release. In the Renografin-76 group there was a 53 +/- 37% increase in lactate release at 10 minutes after contrast agent injection (p less than 0.005), while in the iopamidol patients there was no significant change in lactate release following contrast ventriculography. The increase in lactate release in the Renografin-76 group suggests that myocardial ischemia is induced with this ionic contrast agent. In comparison, the nonionic contrast agent is less toxic to the myocardium and is not associated with the biochemical changes of cellular ischemia.

Aged↗
PubMed1988

The effect of ionic contrast medium on the movement of acutely ischemic and nonischemic canine myocardium.

Regional function assessed by ventriculography may be influenced by the hemodynamic effects of rapidly injecting ionic contrast medium. The importance of this after acute coronary occlusion was examined in eight open-chest, anesthetized dogs. The left anterior descending artery was ligated while sonomicrometric segment lengths in the ischemic (IZ) and nonischemic zones (NZ) were measured. Sodium methylglucamine diatrizoate (Renografin-76, 1 ml/kg) was rapidly injected over 3 seconds. Fifteen minutes later, the left ventricular end-diastolic pressure (LVEDP) was rapidly increased to the level reached during injection. Injecting the contrast increased the LVEDP (7.3 +/- 2.5 to 20.1 +/- 2.9 mm Hg, p less than 0.0001) to the same extent as raising LVEDP (7.6 +/- 2.5 to 10.1 +/- 2.9 mm Hg, p less than 0.0001). Injecting the contrast medium increased IZ total percent systolic shortening (% delta L) (-3.90 +/- 4.43% to -2.68 +/- 4.77%, p less than 0.001) by decreasing isovolumic bulging (-6.68 +/- 4.09% to -5.49 +/- 3.33%, p less than 0.001) with little change in ejection % delta L. NZ total % delta L tended to increase (19.03 +/- 6.53% to 19.94 +/- 6.27%, p = 0.015) because of augmented ejection % delta L (13.12 +/- 2.51% to 13.71 +/- 3.10%, p = 0.017) by the Starling mechanism. Increasing the LVEDP had the same effect on IZ and NZ regional shortening as injecting contrast. Thus regional shortening after acute coronary occlusion is affected by the changes in loading conditions with ionic contrast ventriculography.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Differential accumulation of radiopaque contrast material in acute myocardial infarction.

The differential accumulation of radiographic contrast materials in ischemically damaged and normal myocardium was assessed with direct measurement (fluorescent excitation analysis) of the iodine content of tissue samples from dogs with 48 hour old myocardial infarctions. Tissue samples were obtained 10, 30, 60 and 180 minutes after the intravenous administration of 2 ml/kg body weight of diatrizoate meglumine and sodium (Renografin-76). At all time intervals, the iodine concentration of infarcted tissue was at least threefold greater than that of normal myocardium. At 180 minutes the ratio between iodine concentration in infarcted myocardium and that in normal myocardium was 8.5 and between that in infarcted myocardium and that in blood was 2.6. The iodine concentration in the liver was similar to or greater than that in the infarcted area at time intervals after 10 minutes. These results suggest that the intravenous administration of contrast material may facilitate the identification of acutely infarcted myocardium with computerized X-ray transmission tomography.

Animals↗
PubMed1988

Contrast echocardiography during coronary arteriography in humans: perfusion and anatomic studies.

In humans, the physiologic relation between myocardial blood flow and epicardial coronary artery anatomy remains poorly defined. With the recent development of sonicated microbubble contrast agents, it is now possible to use contrast echocardiography to assess myocardial perfusion and to correlate blood flow with angiographically identified coronary artery anatomy. The purpose of the current study was to determine myocardial perfusion patterns in patients without significant coronary artery disease. The results may be used as a reference to analyze myocardial blood flow in patients with coronary artery disease. Sonicated meglumine sodium diatrizoate solution (Renografin-76), which contains microbubbles measuring 4.5 +/- 2.8 micrograms in diameter by laser analysis, was used as the echocardiographic contrast agent during elective coronary arterriography in 14 patients without significant coronary artery disease. Patients received intracoronary injections of 1.5 to 2 ml of sonicated Renografin-76 without complications. Perfusion characteristics were studied by visual assessment of the two-dimensional echocardiographic images obtained after individual injections. In patients found to be free of significant coronary artery disease by arteriography, the left coronary system always supplied the anteroseptal, anterior, anterolateral and posterior regions of the left ventricle at the mid-papillary, cross-sectional level. The right coronary artery system perfused the inferior and inferoseptal regions in 89% of the patients identified with a right dominant system. The anterolateral papillary muscle was perfused from the left coronary system in all cases. The posteromedial papillary muscle was perfused from the left coronary system in 58% of the patients and from the right system in 42% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1985

Clinical superiority of a new nonionic contrast agent (iopamidol) for cardiac angiography.

The hemodynamic and electrophysiologic alterations induced by ionic contrast agents during cardiac angiography are well described. Recently nonionic contrast agents have become available for cardiac angiography. To evaluate the safety of these new agents, a double-blind randomized study was performed comparing a new nonionic agent (iopamidol) with a commonly used ionic contrast agent (Renografin-76). Eighty-one patients undergoing left ventriculography and coronary angiography were included; 41 received iopamidol and 40 received sodium meglumine diatrizoate (Renografin-76). After left ventriculography, there was a decrease in the arterial pressure with both contrast agents. However, the severity and the duration of hypotension were both significantly greater with Renografin-76 compared with the new nonionic agent (p less than 0.001). After selective injections of the coronary arteries, electrocardiographic analysis demonstrated that the increase in the QT interval (p less than 0.0002) and the changes in both the ST segment and T wave amplitude (p less than 0.001) were significantly greater in the Renografin-76 group compared with the iopamidol group. During coronary angiography, 8 of the 40 patients receiving Renografin-76 required temporary pacing for sinus pauses of 2.5 seconds or more, and 2 of the 40 also developed ventricular fibrillation. None of the 41 patients receiving iopamidol had these complications. This report demonstrates that the electrocardiographic changes, the severity and duration of hypotension and the incidence of serious arrhythmias are significantly greater with Renografin-76 than with iopamidol. Thus, this new nonionic agent appears to enhance the safety of cardiac angiography.

Aged↗
PubMed1989

Effect of atriopeptin II on contrast medium-induced changes in renal blood flow.

Volume expansion has been shown to attenuate the vaso-constrictive effects of contrast medium. Since endogenous circulating levels of atrial natriuretic peptides are elevated during volume expansion and since atrial natriuretic peptides have been shown to blunt or block the vasoconstrictive effects of various pharmacologic agents, we examined the effect of atriopeptin II infusion on contrast medium-induced alterations in renal blood flow. Transient changes in renal blood flow were measured with an electromagnetic flow probe following bolus injections of the contrast medium, sodium meglumine diatrizoate (Renovist II, 2 ml/4 sec), into the renal arteries of dogs. Under control conditions (that is, saline vehicle), the bolus of contrast medium caused an initial 15 to 21% increase in renal blood flow at 14 to 21 seconds, followed by a subsequent 5 to 13% decrease in renal blood flow at 43 to 59 seconds after injection. Infusion of atriopeptin II (0.05 pg/kg/min) into the renal artery did not alter arterial blood pressure, glomerular filtration rate, or baseline renal blood flow, but did produce increases in urine flow rate and clearance of sodium. The infusion of atriopeptin II attenuated the contrast medium-induced reduction in RBF, but the infusion of a threshold dose of bradykinin (1 ng/kg/min) had no effect. These results suggest that low doses of atriopeptin II can selectively attenuate the vasoconstrictive effects of contrast medium on renal blood flow without influencing systemic hemodynamics.

Animals↗
PubMed1977

Fetal uptake of an intravascular radiologic contrast medium.

Trans-placental passage of methylglucamine diatrizoate was studied in 11 human fetuses after intravenous injection to the mother 5 to 49 minutes prior to abortion by hysterotomy. The contrast medium passed the placental barrier and was detected in all fetal tissues measured. No evidence was found of selective uptake by any fetal tissue. The hazards of fetal exposure should be taken into consideration before the administration of intravascular radiographic contrast agents to pregnant women.

Brain↗
PubMed1976

Effects of angiographic contrast media on sino-atrial nodal function.

Injection of meglumine diatrizoate (Renografin-76) into the selectively perfused sinus node artery of the dog produces bradycardia which is unaltered by autonomic blockade or by changes in sinus node artery pressure. Contrast agents and other hyperosmolar substances prolong the R-R interval in proportion to their osmolarity. Selective injection of contrast media into other cannulated segments of the coronary tree produces no change in heart rate. Transfemoral arteriography, however, produces bradycardia with both right and left coronary injections. Both direct and reflex sinus node depression occur with coronary arteriography in the dog. Direct effects are mediated by hyperosmolarity.

Adrenergic beta-Antagonists↗
PubMed1984

The haemodynamic effects of left ventriculography in coronary artery disease and mitral valve disease: a comparison of high and low osmolality contrast media.

We compared the haemodynamic effects of a low osmolality contrast medium Hexabrix 320 (meglumine/sodium ioxaglate) with a high osmolality medium Urografin 370 (meglumine/sodium diatrizoate) in 32 patients. Each underwent left ventriculography with both media, which caused similar small and transient increases in heart rate and systolic pressure. In 15 patients with coronary artery disease, the mean left ventricular end-diastolic pressure increased by 4 mmHg after hexabrix compared with 10 mmHg after urografin (P less than 0.01); it returned to normal more quickly after hexabrix. Changes after both media did not correlate with baseline end-diastolic pressure, ejection fraction, or extent of coronary artery disease, and thus left ventriculography was unhelpful as a stress test. In 14 patients with mitral stenosis, hexabrix produced a smaller increase in left ventricular end-diastolic pressure (P less than 0.001), left atrial pressure (P less than 0.01) and mitral valve gradient (P less than 0.05) than urografin. Patients preferred the low osmolality medium (P less than 0.01). There was no difference in angiographic quality. We advocate low osmolality contrast media for patients with poor left ventricular function or severe mitral stenosis.

Adult↗
PubMedDate not supplied

Slow response induced in canine Purkinje fiber by contrast medium.

Cardiac toxicity of angiographic contrast medium has been documented at the cellular level by using the methods of micro-electrode electrophysiology. Canine Purkinje fibers exposed to contrast medium exhibit a "slow response." The increased automaticity and slowed conduction inherent in this "slow response" may cause the serious arrhythmias and other adverse effects recorded by electrocardiograms during coronary angiography. Hyperosmolarity plays only a minor role in the observed cellular toxicity. The unphysiologic concentrations of sodium, potassium, and calcium in the tested contrast medium were not responsible for the changes observed. Toxicity is probably an inherent chemical property of iodinated diatrizoate or meglumine ions.

Angiocardiography↗
PubMedDate not supplied

Sequential changes in the CT numbers of the normal canine kidney following intravenous contrast administration. I. The renal cortex.

Using a 30-second computed tomography (CT) scanner, the sequential changes in CT numbers of the kidney were determined in three healthy dogs after intravenous administration of sodium and meglumine diatrizoate and iothalamate. For all contrast media, the mean CT number of the cortex was greatest within 2 minutes of rapid intravenous administration. At doses comparable to those used clinically, a linear relationship was demonstrated between the amount of iodine administered (in mg/kg body weight) and the corrected peak mean CT number of the cortex, such that doubling the amount of iodine caused the corrected peak mean CT number of the cortex to approximately double. Following the peak, the mean CT number of the cortex gradually declined. For all contrast media, the corrected mean CT number to corrected peak mean CT number ratios at 5, 10 and 20 minutes were 58 +/- 3%, 39 +/- 3%, and 28 +/- 5% respectively. Our data suggest that rapid-sequence CT may be a valuable tool for evaluating the physiology of renal contrast media excretion.

Animals↗
PubMedDate not supplied

Angiographic nephrectomy using iodinated contrast agent.

Diatrizoate meglumine and sodium (Renografin-76) was perfused in an obstructed renal artery in 13 dogs. Intense and prolonged accumulation of contrast agent ("contrast staining") was achieved in all animals. Repeat injection was frequently necessary to enhance staining. Renin output from the stained kidneys was lower than that from the opposite kidneys. Angiography at 14-18 weeks demonstrated a marked decrease in renal size in all dogs, with complete occlusion of the renal artery in two dogs. No collateral circulation was discerned. Grossly, all experimental kidneys were uniformly shrunken. Histologically, diffuse renal infarction was evident with coagulative necrosis. Contrast staining is an effective method for uniform destruction of renal tissue.

Animals↗
PubMedDate not supplied

A quantitative in vivo comparison of six contrast agents by digital subtraction angiography.

Digital subtraction angiography (DSA) technology can now visualize many significant arterial structures from intravenous injections of contrast media. Image quality of these DSA studies is related to contrast agent enhancement. This study compares contrast agents of differing iodine concentration, viscosity, and osmolarity. A technique is described that utilizes a scanned projection digital radiographic system to compare quantitatively degrees of intra-arterial opacification after the administration of six intravenous contrast agents: iothalamate (at four different concentrations and in combinations with two different cations), diatrizoate, and ioxaglate. The quantitative arterial enhancement was compared in dogs utilizing an extra-period latin-square multiple change-over clinical trial design. The contrast agents span a range of organically bound iodine from 282 mg I/ml. When rate and volume of contrast agent injected are held constant, intra-arterial opacification is directly a function of the iodine concentration (mg I/ml) of the agent injected, while osmolarity and viscosity have no effect on opacification. These studies support the use of agents with high iodine concentration for maximum vascular visualization.

Angiography↗
PubMedDate not supplied

Mechanism of the renal response to contrast medium in dogs. Decrease in renal function due to hypertonicity.

Radiographic contrast media (CM) (meglumine/sodium diatrizoate-76%; 1650 mOsm/kg) and other hypertonic solutions induce renal vasoconstriction by an unknown mechanism. In anesthetized dogs, renal blood flow (RBF) was measured with an electromagnetic flowmeter and filtration fraction (FF) and glomerular filtration rate (GFR) by the renal extraction of technetium-99m tin chelate. Ureteral pressure (UP) and wedged renal venous pressure (VP) were measured as indices of intrarenal pressure. Measurements of renal length (L), along with pressures, made it possible to examine the compliance of the system. A 4-cc intrarenal bolus of CM caused a 59% reduction in GFR (control: 0.63 +/- 0.04 to 0.26 +/- 0.04 ml/min X g, mean +/- SEM), in association with a 23% reduction in RBF (control: 3.10 +/- 0.11 to 2.39 +/- 0.26 ml/min X g) and a 44% decrease in FF (control: 0.32 +/- 0.01 to 0.18 +/- 0.03). These responses were compared with a 3-microgram intrarenal bolus of norepinephrine (NOREPI) which resulted in a 79.0 +/- 7.5% reduction in RBF, 68.3 +/- 7.3% reduction in GFR and 42.6 +/- 15.6% increase in FF. The NOREPI-induced vasoconstriction caused transient decreases in renal L, UP, and VP, whereas the CM-induced decrease in renal blood flow was associated with increases in these parameters. In studies employing ureteral occlusion to elevate intrarenal pressure, the magnitude (area, cm2) of the CM-induced decrease in renal perfusion was accentuated with increased UP (r = 0.79, n = 24, P less than 0.001). The CM-induced increase in renal L, UP, and VP must reflect osmotic forces and an increase in intrarenal pressure. The decreases in FF and GFR probably reflect Starling forces in the glomerular capillaries, with osmotic transients dominating. The results suggest a mechanical mechanism for the CM-induced decrease in RBF.

Acetylcholine↗
PubMedDate not supplied

Perfluoroctylbromide. Acute hemodynamic effects, in pigs, of intravenous administration compared with the standard ionic contrast media.

Perfluoroctylbromide (PFOB) is a relatively new noniodinated contrast media that, after intravenous administration, produces prolonged opacification of the blood pool and subsequently selectively enhances the liver and spleen on computed tomography. There has been concern regarding the hemodynamic effect of this agent but little actual knowledge exists in this regard. Accordingly, the acute transient hemodynamic effects of PFOB emulsion were evaluated in five pigs and compared with the standard ionic contrast agent meglumine sodium diatrizoate (Renografin-76). Left ventricular (LV) pressure, internal diameter, and wall thickness were monitored during the alternate intravenous administration of 930 mg/ml PFOB and 370 mg/ml R-76 at a rate of 20 mls/second for a total volume of 1 ml/kg body weight. Renografin-76 caused a significant decrease in LV pressure and dp/dt (rate of change of LV pressure), and an increase in LV end-systolic diameter and a decrease in LV end-diastolic wall thickness. PFOB caused no change in LV pressure and dimensions. Thus, rapid intravenous administration of PFOB does not induce significant acute alterations in left ventricular pressure, dp/dt, dimension, or wall thickness.

Animals↗
PubMedDate not supplied

The effect of ion composition on cellular membrane potentials during selective coronary arteriography.

An animal experimental study on seven thoracotomized dogs was designed to investigate the effects of intracoronarily injected sodium meglumine diatrizoate on myocardial electrophysiology and to evaluate the contribution of the corresponding changes of electrolyte levels in coronary blood. For this purpose the effects of alterations in the Na+-, K+- and Ca++-concentrations in coronary blood were studied separately by intracoronarily injected model solutions. Membrane potentials were recorded from the left ventricular myocardium by a modified microelectrode technique which is applicable to the beating and blood perfused heart in situ. Following selective coronary arteriography there was a temporary hyperpolarization of resting potentials and a prolongation of action potentials which may be explained by a contrast-induced local deficiency of potassium and calcium ions and by a relative prevalence of sodium ions in coronary blood. In selective coronary arteriography the synchronicity of cardiac excitation is disturbed by the regional prolongation of action potentials, which may induce ventricular arrhythmias.

Action Potentials↗