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Biomedical subjects

H W Fischer

Publications and source records attributed to H W Fischer.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

Nephrotoxicity of sodium iopanoate in hydrated and dehydrated dogs.

The nephrotoxic effect of sodium iopanoate, infused intravenously in dosages of 1.5, 3 and 6 g over a 2-hour period in eight dogs (22--27 kg) in both the hydrated and dehydrated stages, were investigated. On biochemical, hemodynamic and morphological studies, the nephrotoxic effect was found to be clearly dose-dependent and greater in the dehydrated stage. Previously suggested mechanisms for acute renal failure, such as a direct tubular toxicity, tubular obstruction and hypotension, could not be supported as main factors in the development of acute renal failure post-cholecystography, although they might well have a contributory effect. The primary cause of renal failure post-cholecystography cannot be determined unequivocally from this investigation. However, the observed findings would appear to be consistent with a toxic effect of iopanoate in the small vessels possibly resulting in ischemic tubular necrosis.

Acute Kidney Injury↗
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Biliary excretion of iodipamide and iodoxamate in normal and common bile duct-obstructed dogs.

Iodipamide and iodoxamate were compared at equimolar clinical dosages in dogs with normal, incompletely obstructed and completely obstructed common bile ducts. Forty-eight experiments were performed under general anesthesia in six cholecystomized chronic bile fistula dogs. The peak biliary iodoxamate excretion rate, but not the peak bile iodoxamate concentration, was significantly higher with normal and incompletely obstructed common bile ducts. In complete obstruction, both a significantly higher total biliary iodoxamate excretion and concentration were obtained, but this was still insufficient for radiographic opacification by conventional technique. Lesser toxicity of iodoxamate is suggested by its significantly lower serum levels, its higher bile: urine excretion ratio and its faster compensatory urinary excretion in complete common bile duct obstruction. Iodoxamate appears on this evidence to be a better cholangiographic contrast agent than iodipamide.

Animals↗
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Epinephrine enhanced knee arthrography.

The effect of .3 cc of 1:1000 epinephrine on iodine concentration, total iodine content, fluid volume and radiographic quality was evaluated in knee arthrograms in dogs. With the addition of epinephrine the iodine concentration and total iodine content were significantly higher initially and remained significantly higher than in controls over a one hour period. The fluid volume in the knee was significantly lower with epinephrine. Initially both contrast absorption and dilution have major effects in decreasing iodine concentration. With increasing time the effect of contrast absorption becomes the major factor, having a two of three times greater effect on decreasing iodine concentration. With epinephrine radiographs were judged significantly better early and while the quality deteriorated rapidly in the controls the enhanced quality with epinephrine persisted up to one hour. Epinephrine is a very useful adjunct in enhancing the quality of knee arthrography.

Animals↗
PubMedDate not supplied

Deleterious synergism of a cardiac glycoside and sodium diatrizoate.

Studies were performed in mice to determine if the cardiac glycoside, Strophanthin-K, and the contrast medium, sodium diatrizoate, interact synergistically to produce death. Intravenous injections of lethal and near lethal doses of the two agents produced a significantly greater mortality than the individual agents alone. Low or near clinical doses of Strophanthin-K, when given with doses of diatrizoate in the lethal range, produced mortalities significantly greater than did the diatrizoate alone. Similarly, low or near clinical doses of diatrizoate given with doses of Strophanthin-K in the lethal range produced mortalities significantly greater than for the Strophanthin-K alone. Isotonic or hypertonic saline, when substituted for diatrizoate or Strophanthin-K did not produce synergistic increases in mortality. Thus neither the injection volume, nor agent hypertonicity or ionic strength, seem to be the primary factors in the synergism to produce death. The diatrizoate anion appears to be an important factor. Until more information is available from other animal models it appears that patients receiving cardiac glycoside should be considered to have a higher than normal risk of serious reactions to contrast media in intravenous urography.

Animals↗
PubMedDate not supplied

Contrast media in coronary arteriography: a review.

Much knowledge of coronary artery disease and much of the progress in surgical treatment of coronary artery disease has been directly dependent upon the safety with which coronary arteriography has been performed. This safety depends upon the ease of placing the contrast media in the arteries and on the toxicity of the contrast medium itself. This review deals with contrast media toxicity in coronary arteriography, as distinct from toxicity in angiocardiography and other angiography.

Angiocardiography↗
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Protein binding to iothalamate ethyl ester.

A major problem in the development of a particulate hepatolienographic agent is the prevention of particle aggregation upon contact with blood. When iothalamate ethyl ester, a particulate suspension for potential use as an hepatolienographic agent, was mixed with human or animal plasmas, it resulted in moderate to severe flocculation. In a study conducted to define the binding of plasma proteins to the iothalamate ethyl ester particles, plasma was reversibly adsorbed to various particle preparations. Fractions obtained by incubation of the particle-plasma complexes in buffers of increased ionic strength and decreased pH were subjected to polyacrylamide disc gel electrophoresis. The fraction containing the specifically bound proteins produced three distinct bands corresponding to prealbumin, albumin, and fibrinogen. Since the particles flocculated only when mixed with plasma, it is postulated that the fibrinogen-particle interaction is a major factor leading to particle agglutination.

Blood Proteins↗
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Biliary excretion of iodipamide and iodoxamate in dogs with hepatic dysfunction induced by oral administration of dimethylnitrosamine.

Iodipamide and iodoxamate were compared in equimolar clinical dosages in five cholecystectomized chronic bile fistula dogs in which hepatic dysfunction was produced by oral administration of a total dose of 480 and 960 microliters dimethylnitrosamine (DMNA), respectively. After both DMNA dosages, the peak biliary excretion rate for iodoxamate was significantly higher than for iodipamide (p less than 0.01). The peak bile iodine concentration was not significantly different for the two agents (480 microliter DMNA: p less than 0.1; 960 microliter DMNA: p = 0.07). On the basis of this investigation, it is suggested that iodoxamate should not significantly improve the opacification of the biliary system in patients with hepatic dysfunction.

Animals↗
PubMedDate not supplied

The effect of bilirubin on biliary iodipamide excretion in the dog.

The effect of bilirubin on biliary iodipamide excretion and concentration was investigated in cholecystectomized dogs during complete bile diversion and constant bile salt replacement. A significant dose-dependent depression of both biliary iodipamide excretion rate and bile iodipamide concentration was found with increasing bilirubin dose. Whether or not bilirubin was infused at a constant of 0.1 mu moles/min/kg, the excretion rate and bile concentration of iodipamide was greatest with the largest 5.2 mu moles/min/kg iodipamide dose. Iodipamide had no significant effect on the bilirubin excretion rate, but because of its highly choleretic nature it had a dilution effect on the bilirubin bile concentration. This investigation suggests that a reduction of the iodipamide blood levels by either decreasing the dose or prolonging the infusion time will lead to poorer radiographic visualization of the biliary system in patients with unconjugated hyperbilirubinemia (prehepatic jaundice).

Animals↗
PubMedDate not supplied

The need for more study of gastrointestinal contrast media.

After four score years of alimentary tract radiology based on barium sulfate, we have little agreement on the proper characteristics of the contrast agent for visualization of the esophagus, stomach, duodenum, and colon, nor have we had any viable replacements, organic or inorganic, for barium sulfate. A number of characteristics of barium sulfate preparations have been examined. A positive charge on the particle is not of advantage in mucosal coating, but viscosity seems to be important. Particle size is probably not important. Suspension stability is probably overrated. Much, if not most, of the properties of barium sulfate preparations depend on the surface active agents, the so-called additives. The thickness of barium sulfate coating necessary for surface visualization under clinical conditions is defined. Some preliminary data on a new barium preparation is reported.

Animals↗
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Particulate contrast media for computed tomographic scanning of the liver.

A contrast agent that is selectively accumulated in the liver should greatly improve the diagnostic value of contrast enhanced CT scanning. The advantages and disadvantages of different classes of hepatographic agents are briefly reviewed. Experimental results obtained with the particulate contrast agents, iothalamate ethyl ester and iodipamide ethyl ester, are presented in more detail. Following intravenous infusion of iodipamide ethyl ester, approximately 60% of the injected dose is accumulated in the rat liver. CT scanning experiments involving iothalamate ethyl ester infusions in New Zealand White rabbits demonstrate significantly higher liver contrast enhancement at 10-30 minutes postinfusion than is observed with diatrizoate at a sixfold greater iodine dose. The selective accumulation of a particulate contrast agent in hepatic reticuloendothelial cells compared to virtually no accumulation in implanted VX2 carcinoma demonstrates the important potential value of these agents in improving detection of liver metastases.

Animals↗
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Cardiovascular radiology. Possible factors in intravascular contrast media toxicity.

(I.) Toxicity of ionic coronary arteriography contrast media has been shown to depend on their cationic and anionic composition and their osmolality. Using a right coronary injection technique in the dog, the authors have shown a relationship between toxicity as manifested by occurrence of ventricular fibrillation and the presence of calcium binders in the contrast media. Sodium citrate and EDTA have been identified as the specific agents in certain contrast media that significantly increase the incidence of fibrillation in laboratory experiments. (II.) A deleterious synergism between water-soluble angiographic and urographic media and digitalis compounds has now been demonstrated, based on mortality studies (LD50) using bolus intravenous injections in white mice. The testing of a number of other classes of drugs for a similar effect has shown thus far that only the digitalis class exhibits this synergism. Surprisingly, the nonionic contrast medium, metrizamide, has been shown to have a greater synergistic effect with digitalis drugs than diatrizoate ionic media. (III.) In dog experiments under Nembutal anesthesia in which aortic flow, pulmonary artery and vein pressures, systemic arterial pressure, and EKG were monitored, left atrial pressure increases as soon as or before pulmonary artery pressure rises, even at low doses of ionic contrast media administered intravenously. This may indicate 1) flow to the left heart increases dramatically, or 2) there is a very early myocardial depression. The significance of the above findings and application to clinical practice will be discussed.

Angiography↗
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New media. Particulate contrast media.

Particulate contrast agents, when compared to water-soluble media, offer the advantage of allowing the administration of high doses without creating hypertonicity gradients and ionic imbalances. Since these radiopaque particles are accumulated in the reticuloendothelial system, they could be ideal hepatic CT contrast agents. We have developed a method for making particles of 2 +/- 1 microns by precipitating from an organic solvent. Preincubation of these particles in human serum albumin overcomes the very serious problem of in vivo particle aggregation and embolization. The ethyl esters of iothalamic and iodipamic acid have been injected intravenously into mice, rats, and rabbits. Radiopacification of the liver is maximal within 2-3 hours postinfusion, with radiopaque material subsequently clearing through the biliary system. Elimination from the organism seems to be complete within a few days postinfusion. Efforts to decrease the subacute toxicity of these agents are underway.

Animals↗
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Biodistribution of a particulate hepatolienographic CT contrast agent: a study of iodipamide ethyl ester in the rat.

Particulate contrast agents have been shown to be efficacious in computerized tomographic detection of liver tumors. This article quantitatively defines the biodistribution of the experimental particulate agent iodipamide ethyl ester in the rat as a function of time after intravenous infusion. The contrast agent is actively accumulated in the liver and spleen with high selectivity compared to iodine concentrations in the blood or other organs. The contrast material remains at high concentration in the liver for more than 2 hours and then is slowly cleared from the organism in approximately two days. The high selectivity and retention of contrast in the liver are indicative of the value of particulate agents in contrast-enhanced computerized tomography.

Animals↗
PubMedDate not supplied

Failure of iosulamide to enhance hepatic tumors in rats.

Iosulamide, an experimental cholangiographic agent recently being evaluated for hepatic contrast enhancement in computed tomography, has been investigated in the rat for the differential enhancement between the liver and three histologically different experimental tumors (a well differentiated mammary adenocarcinoma, a poorly differentiated colon carcinoma, and a hepatoma). After intravenous injection of iosulamide in dosages of 140 and 280 mg iodine per kg, iodine concentrations were determined in blood, liver and tumors at 1, 5, 10, and 30 minutes, using x-ray energy spectrometry. Compared with the surrounding liver parenchyma, the iodine concentrations were generally higher in the breast carcinoma. With respect to the liver, iodine concentrations varied greatly in the colon carcinoma and hepatoma. The iodine washout from all three tumors was relatively slow. Since the distribution volume of cholangiographic contrast agents includes both vascular and interstitial space, the relatively high and prolonged iosulamide accumulation in tumors can be explained by a relatively large interstitial compartment, which is apparently characteristic of neoplastic lesions. This, together with the modest iodine concentrations found in the liver, suggests that iosulamide is of little use in computed tomography for the differential enhancement of liver and hepatic tumors.

Adenocarcinoma↗
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Calcium binding by radiopaque media.

This study quantified the binding of ionic calcium by contrast media with disodium edetate and trisodium citrate versus those with only calcium disodium edetate. First, calcium binding by sodium diatrizoate with calcium disodium edetate was measured using an ion-selective electrode at ionic strengths of .08, .16, and .80 molal. Significant binding of calcium was observed, and the probable reaction product is calcium chloride diatrizoate. Second, solutions were mixed containing Renografin 76 (or Hypaque 76) and NaCl at a physiologic ionic strength. The Renografin, which contains disodium edetate and trisodium citrate, caused significantly more binding than did the Hypaque. However, 60% of the drop in ionic calcium was observed with Hypaque and is related to the diatrizoate anion. The nonionic agent iopamidol produced no decrease in ionic calcium. Significant reductions in ionic calcium are produced by both the diatrizoate anion and by edetate and citrate additives.

Calcium↗