Christopher R.J. Mladinich

Short-term Effects of Selective Renal Arterial Carbon Dioxide Administration on the Dog Kidney

PURPOSE The authors examined the nephrotoxicity of carbon dioxide injected directly into the renal arteries as an arterial contrast agent. MATERIALS AND METHODS Fourteen anesthetized dogs received selective renal infusions of CO2 ranging from a normal dose of 7 cm3/kg to high doses of 11-54 cm3/kg. Two dogs received conventional iodinated contrast media. The effects on renal function and histologic appearance were evaluated by means of radionuclide studies (iodine-131 iodohippurate sodium and technetium-99m dimercaptosuccinate) and histopathologic examination (light, transmission, and scanning electron microscopy). RESULTS Although there was a mean decrease in renal blood flow of 11.86% (standard error [SE], 7.1) immediately after the injection of CO2, flow had returned to baseline (0.17%; SE, 5.27) after 24 hours. Although the sample size was small, there was no dose-dependent effect of CO2 on renal function and histologic appearance. Mild histologic changes and one case of moderate acute tubular necrosis were seen only in cases in which the kidney was positioned vertically rather than laterally. CONCLUSION Although formal studies in patients are required, the results of this investigation suggest that CO2 may be a safe contrast agent and less nephrotoxic than existing contrast agents, providing care is taken to ensure that CO2 is not trapped in a vertically positioned kidney, as might occur in renal transplant recipients.

In vivo animal tests of an artifact-free contrast agent for gastrointestinal MRI.

A variety of shortcomings are associated with most currently used gastrointestinal contrast agents for magnetic resonance imaging (MRI). Artifacts resulting from peristalsis and other motions in the abdominal region are produced by many positive contrast agents (which increase signal intensity). Although this is not a problem for negative contrast agents (which decrease signal intensity), some negative contrast agents produce magnetic susceptibility artifacts that are especially pronounced at high field strength and with gradient echo pulse sequences. These susceptibility artifacts are produced by both paramagnetic and diamagnetic agents. It has been demonstrated in phantoms, however, that susceptibility matching can be used to produce contrast agents with desirable relaxation and contrast properties but without deleterious susceptibility artifacts. We now report results of animal tests of such an oral contrast agent, consisting of a suspension of superparamagnetic iron oxide particles and diamagnetic barium sulfate particles, compared to individual suspensions of the iron oxide and of the barium sulfate. Iron oxide was the least effective and the matched susceptibility mixture was the most effective for the intestine, which has traditionally been the most difficult region of the GI tract to visualize clearly. Matched susceptibility mixtures, which are inherently able to yield images free of susceptibility artifacts without compromising contrast, show promise of being improved oral negative contrast agents for use in gastrointestinal MRI.

In vivo MR evaluation of Gd-DTPA conjugated to dextran in normal rabbits.

A dextran-Gd-DTPA compound has been recently synthesized utilizing 70,800 Da molecular weight dextran. This polymeric contrast agent for magnetic resonance imaging has been found chemically to be very stable and to demonstrate in vitro improved relaxivities of 1.5 to 2.3 times that of monomeric Gd-DTPA at 100 MHz. This MR experiment examines the in vivo distribution and relaxivity of the 70,800 Da molecular weight dextran-Gd-DTPA compound in a rabbit model by measuring the change in signal-to-noise ratio of a variety of organs (renal cortex, renal medulla, liver, brain, and torcula herophile) compared to the preinjection state. Results demonstrate prolonged (beyond 60 min) enhancement of the renal cortex, renal medulla, liver and torcula, and no enhancement of brain parenchyma.

Rate-Dependent Block in the Sinus Venosa of the Swine Heart during Transverse Right Atrial Activation: Correlation Between Electrophysiologic and Anatomic Findings

Introduction: Whether the crista terminalis or the sinus venosa result in rate‐dependent block during transverse activation of the right atrial activation remains unknown. In the present study, right atrial activation at different cycle lengths was studied in the swine heart using high‐resolution noncontact mapping (Endocardial Solutions). The location of the block was tagged and correlated with postmortem anatomical findings.

Carbon dioxide as an angioscopic medium. Comparison to various methods of saline delivery.

The limitations of angiography, when it is used as the sole method of vascular assessment, are increasingly apparent as vascular intervention becomes more sophisticated. Angioscopy could be an adjunctive diagnostic modality by differentiating among thrombus, dissection, and atheroma, and by monitoring the response to therapy. However, angioscopy requires a blood-free field for adequate visibility, and this may be difficult to obtain. The feasibility of carbon dioxide (CO2) and various saline delivery methods for clarifying the viewing field for percutaneous angioscopy was investigated. Angioscopy of femoral and iliac arteries on nine dogs was performed. Saline was infused by hand injection, pressure bag infusion, or mechanical power injection, and CO2 gas was injected using a special gas injector. The clarity of the viewing field was graded for each medium and method. Excellent quality antegrade femoral angioscopy was obtained with CO2. The superiority of CO2 injection in comparison with power-injected saline approached statistical significance (P = .06). Power-injected CO2 and power saline were superior to hand-injected or pressure bag-injected saline for maintaining sufficient visibility. Retrograde iliac angioscopy was possible without inflow occlusion, but required high flow rates (only possible with power-injected saline or CO2). CO2 injected under controlled circumstances holds promise as a medium to improve angioscopic visibility.

Comparison of Hepatic Damage from Direct Injections of Iodinated Contrast Agents and Carbon Dioxide

PURPOSE This study guides the choice of contrast agent for localization of portal veins during transjugular intrahepatic portosystemic shunt (TIPS) placement or use in percutaneous transhepatic cholangiography (PTC) by providing gross anatomic and histologic comparison of effects from parenchymal injections of iodinated contrast agents and carbon dioxide. MATERIALS AND METHODS Eighteen New Zealand White rabbits received direct injections of 2-5 mL of either the nonionic contrast agent iohexol 300 mgI or the ionic contrast agent diatrizoate meglumine 60% into one lobe of the liver and the same volume of CO2 into the other lobe. The rabbits were killed at 2-7 days for gross and histologic evaluation of the livers. RESULTS At the time of injection, the diatrizoate and iohexol sites showed persistent dark discoloration, whereas CO2 sites showed minimal visible changes. On gross examination at death, all diatrizoate sites showed severe scarring and also commonly showed areas of necrosis. CO2 and iohexol sites showed only minimal discoloration and needle-puncture scars (P < .0001). The histologic grade for diatrizoate sites was significantly more severe than paired CO2 sites (P < .016). Iohexol sites showed mild histologic changes similar to paired CO2 sites (P = .375). CONCLUSION Iohexol and CO2 produce less severe hepatic damage and are preferred to meglumine diatrizoate for hepatic injection.

Effects of Carbon Dioxide Arterial Infusion on Hepatic Biochemistry and Histology in a Rabbit Model

RATIONALE AND OBJECTIVES.The objective of this study was to determine the effect of carbon dioxide (CO2) infusion on hepatic biochemistry and histology in a rabbit model. METHODS.The study population consisted of 24 anesthetized rabbits that received hepatic infusion of either CO2 or saline (control) at doses of 10 mL/kg, comparable with those doses used in human clinical trials. Blood for clinical chemistry analysis was collected at baseline, 1 hour, 24 hours, and 168 hours (7 days) postprocedure. The rabbits were killed at 7 days postprocedure and the liver examined histologically for hepatic damage. RESULTS.There were no significant differences between the CO2 and the control groups in dorsal, ventral, and dorsal/ventral scores. Increases in alanine, an important indicator of hepatocellular membrane injury, in the CO2 group were significantly greater at 1 hour and 24 hours posttreatment (P = 0.037 and 0.013). However, the mean levels at 168 hours (7 days) were not significantly different (P = 0.22). The increases at 1 and 24 hours were small, transient, and considered clinically insignificant. CONCLUSION.No long-term hepatic effects in these animals were suggested by biochemical and histological examinations.

Contribution of the vertebral artery to cerebral circulation in the rat snake Elaphe obsoleta

Blood supplying the brain in vertebrates is carried primarily by the carotid vasculature. In most mammals, cerebral blood flow is supplemented by the vertebral arteries, which anastomose with the carotids at the base of the brain. In other tetrapods, cerebral blood is generally believed to be supplied exclusively by the carotid vasculature, and the vertebral arteries are usually described as disappearing into the dorsal musculature between the heart and head. There have been several reports of a vertebral artery connection with the cephalic vasculature in snakes. We measured regional blood flows using fluorescently labeled microspheres and demonstrated that the vertebral artery contributes a small but significant fraction of cerebral blood flow (∼13% of total) in the rat snake Elaphe obsoleta. Vascular casts of the anterior vessels revealed that the vertebral artery connection is indirect, through multiple anastomoses with the inferior spinal artery, which connects with the carotid vasculature near the base of the skull. Using digital subtraction angiography, fluoroscopy, and direct observations of flow in isolated vessels, we confirmed that blood in the inferior spinal artery flows craniad from a point anterior to the vertebral artery connections. Such collateral blood supply could potentially contribute to the maintenance of cerebral circulation during circumstances when craniad blood flow is compromised, e.g., during the gravitational stress of climbing. J. Morphol. 238:39–51, 1998.

Evaluations of the renal cell carcinoma model Caki-1 using a silicon based microvascular casting technique.

The vascular development of orthotopically grown human renal cell carcinoma (Caki-1) was examined using a silicon based casting technique in nude mice. Images taken of these vascular casts showed Caki-1 tumors to be highly vascularized and invasive. The spread of the tumor within the cortex of the kidney revealed that Caki-1 recruits the kidneys own vasculature, destroying the functional glomeruli in the process. The loss of these glomeruli was further highlighted by the presence of enlarged glomeruli resulting from the development of super nephrons. Vessel size and density measurements were then made in this model. This was done using both computer-based and manual measurement methods. In the vessel size studies the computer-based method tended to overestimate the number of larger diameter vessels whereas the vessels density assessment showed good agreement between the two techniques. Nevertheless, both methods showed that Caki-1 tumors possessed a higher proportion of larger diameter vessels and a lower vessel density than normal kidney cortex. In summary, silicon based vascular casting proved to be a simple and effective tool for the study of tumor vasculature. In particular this technique could readily be used to examine the invasion of tumor into normal tissue. The computer-based technique for evaluating vessel number and vascular density was found to have merit in both normal and tumor tissues, particularly in the vascular density studies. However, in both settings this technique did tend to overestimate the number of larger diameter vessels.