James L. Barnhart

A feasibility study on quantitating myocardial perfusion with Albunex®, an ultrasonic contrast agent

Quantitating regional myocardial perfusion has been the much sought-after but still elusive goal of many intensive investigations over the years. Videodensitometry of the variation of myocardial echogenicity in two-dimensional (2-D) echocardiograms as a function of time in conjunction with the injection of a bolus of an ultrasound contrast agent has been used clinically as a tool for a direct assessment of regional myocardial perfusion, despite that the precise relationship between tissue echogenicity observed on an image and the echoes detected by the ultrasonic probe is unknown. A study was undertaken to determine whether ultrasonic backscatter calculated from unprocessed radio frequency (RF) echoes returned from myocardium could be used to quantitate regional myocardium perfusion. A real-time ultrasonic scanner has been modified and interfaced to a microcomputer to acquire RF data at a rate up to 10 frames per second. Preliminary experimental data were obtained from four open-chest dogs following intracoronary injection of a bolus of Albunex and two dogs following intravenous injection with this modified scanner. On one hand, these results indicate that the integrated backscatter measured from the region of myocardium perfused by the coronary artery where Albunex is injected and selected for monitoring initially increases, reaches a peak, and then decreases as the contrast agent is washed out and that the magnitude of the peak is approximately linearly proportional to the volume concentration of Albunex microspheres injected, clearly demonstrating the feasibility of this approach for quantitating region myocardial perfusion. On the other hand, intravenous injections did not result in any appreciable change in myocardial backscatter in the left ventricle although a response could be observed in the left ventricular blood pool.

Influence of paramagnetic ions and pH on proton NMR relaxation of biologic fluids.

The extent to which various concentrations of the paramagnetic metal ions [gadolinium (III), manganese (II), chromium (III), iron (III), nickel (II), copper (II), and cobalt (II)] affect proton magnetic relaxation times of distilled water, 4% human serum albumin (HSA), and dog plasma was studied in vitro. The pH of water and HSA varied from 4 to 8. Nuclear magnetic resonance relaxation parameters, T1 and T2, were measured at 10.7 MHz using inversion recovery and spin-echo radiofrequency sequences, respectively. The presence of Mn(II), Gd(III) and Cr(III) in water significantly reduced T1, while Fe(III), Ni(II), Cu(II) and Co(II) had only a minimal effect. In 4% HSA and dog plasma Mn(II) and Cu(II) had the greatest effect on T1. At neutral pH, Gd(III) and Cr(III) had little effect on T1, while Mn(II) induced a large shortening of T1. All of the metal ions changed T2 less than T1. These differences in proton relaxation enhancement caused by the various ions in the three solutions studied are due to variations in the effective magnetic moment, the degree of binding of the ions to protein, and the chemical form of the ion associated with changes in pH. Thus, it is impossible to predict the effect of metal ions on proton relaxation in vivo based solely on in vitro studies, because of the complexity of various biologic fluids in vivo.

Urinary excretion of dye in dogs infused with BSP or its glutathione conjugate

Renal clearance of BSP compounds was investigated in dogs during infusion of sulfobromophthalein (BSP) or its glutathione conjugate (BSP-GSH). Conjugated BSP compounds are more readily excreted into urine than unconjugated BSP. Dye clearance into urine was much less than simultaneously measured inulin clearance. This suggests that protein binding of BSP compounds significantly retards the glomerular filtration of the dye. BSP was found to bind more avidly to albumin than BSP-GSH. The ratio of dye clearance to inulin clearance remained relatively constant over a broad range of plasma concentrations of dye. The data support but do not prove glomerular filtration of non-protein-bound dye as the major mechanism accounting for urinary elimination of BSP compounds in the dog.

Characteristics common to choleretic increments of bile induced by theophylline, glucagon and SQ-20009 in the dog.

Summary Theophylline, glucagon, and SQ-20009 induce a choleresis in the dog characterized by a proportionate increase in erythritol clearance and bile flow, no increase in bile salt excretion, and by an isosmotic solution of similar electrolyte composition. The increment in bile appears to originate at the canaliculus in response to increased cyclic-AMP. The authors are indebted to Ruthie Pettigrew and Mark Hardt for valuable technical assistance and to Dorothy Bass for preparation of the manuscript.

Does glucagon enhance opacification of the bile ducts during intravenous cholangiography? An experimental study in dogs.

To determine the rational for the ability of glucagon to enhance opacification of the bile ducts during intravenous cholangiography, which has been claimed in recent clinical reports, experiments were performed in dogs which had had Thomas cannulas inserted. A constant step-wise infusion of iodipamide was administered with or without a bolus injection and constant infusion of glucagon. At every infusion rate of iodipamide the biliary concentration of the contrast agent was less when glucagon was administered. Glucagon caused a choleresis, but had no effect on the rate of excretion of iodipamide. It is concluded that the theory that glucagon is of value to improve opacification of the bile ducts during intravenous cholangiography is unlikely to be confirmed by further clinical trials.

The potential of iosulamide meglumine as a contrast material for intravenous cholangiography: an experimental study in dogs.

Because of relatively low acute toxicity, iosulamide meglumine has been recommended as an improved contrast material for intravenous cholangiography. It has been postulated that high doses of the compound could be given safely with the expectation of achieving greater biliary excretion and improved opacification of the biliary tree. Experiments performed in dogs show that higher rates of infusion of iosulamide result in greater urinary elimination without additional biliary excretion. Consequently, iosulamide is unlikely to have any special advantage as a contrast agent.

Changes in bile flow and composition induced by radiographic contrast materials.

The hepatic excretion of radiographic contrast materials has a major impact on the composition and volume of bile. One obvious effect is the presence of the contrast agent in bile at a concentration that is determined by the rate of hepatic excretion, the rate of basal bile flow, and the rate of bile flow induced by the biliary excretion of the contrast agent. The magnitude of the choleretic response associated with the biliary transfer of contrast materials varies over a wide range. Iopanoic acid does not increase bile flow, whole RCK-136, an experimental contrast material that is similar to iopanoic acid chemically (both are triiodophenyl alkanoates), is a potent choleretic, generating 44 microliter of bile for each mumol excreted into bile. In distinction, the contrast materials in another chemical class, the dimers of triiodobenzoic acid, increase bile flow, but over a narrow range (20-25 microliter/mumol). The changes in bile flow and composition accompanying the administration of iodoxamate, one of the compounds of the dimer type, were compared to the choleresis induced by taurocholate. The additional bile flow was canalicular in origin in both instances, but the electrolyte composition of the bile was different. Bicarbonate concentration in the iodoxamate-induced increment of bile was nearly twice the concentration of bicarbonate in bile stimulated by taurocholate (52.3 and 25.3 mEq/1, respectively). This suggests a canalicular mechanism for iodoxamate-stimulated bicarbonate entry into the bile. The characteristics of bile induced by iodoxamate were also compared to bile associated with a variety of other choleretic agents, including diethyl maleate, DBcAMP, SC2644, and secretin. Only SC2644 stimulated canalicular bile flow with a high bicarbonate concentration similar to iodoxamate.