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OBJECTIVE: The aim of this study was to evaluate the differences of the in vivo efficacies of Levovist(SH U 508 A) and Albunex, air-based contrast agents (CAs) with different shell materials, by direct comparison. METHODS: SH U 508 A, 300 mg/ml, and Albunex were injected intravenously at doses of 0.1 and 0.15 ml/kg, respectively, into the same dogs (n=6). Contrast enhancement in the left ventricle was evaluated visually and by off-line measurement of brightness. RESULTS: Both CAs yielded good peak contrast, while the duration of contrast enhancement with SH U 508 A was seven times that with Albunex. With Albunex, reduction of contrast enhancement at end-systole and in the late phase of diastole during one heartbeat was observed, and a positive correlation was observed between contrast enhancement and heart rate. Contrast enhancement was nearly constant during one heartbeat with SH U 508 A. CONCLUSION: SH U 508 A yielded consistent and longer contrast enhancement in the left ventricle than Albunex under the same conditions.

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The aim of this study was to evaluate in vivo kinetics of microbubbles of SH U 508 A, in comparison with Indocyanine Green, a dye used as an indicator of blood flow. Microbubble kinetics were evaluated in various vessels (i.e., vena cava, aorta, renal artery, renal vein and portal vein) in rabbits after injection of SH U 508 A by measuring Doppler signals (n = 5). The kinetics of Indocyanine Green were evaluated by measuring absorbance using a photodiode (n = 5). Test substances (SH U 508 A 300 mg/mL and Indocyanine Green 1.25 mg/mL) were injected IV at a dose of 0.1 mL/kg B.W. Peak signal intensity was observed immediately after injection of SH U 508 A, followed by biphasic decay. The rates of biphasic decay were similar in all vessels. A second peak of the signal, which indicated recirculation of the microbubbles, was observed in the vena cava. The circulation and recirculation times of the microbubbles after injection of SH U 508 A were similar to that of Indocyanine Green. These findings suggest that the majority of SH U 508 A microbubbles circulate through the body similarly to blood flow, without retention, in the vasculature.

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In the present report, a "color-filled pattern", the late phase effect in the intra-venous contrast enhanced color Doppler sonography is introduced, using SH/TA-508 as the contrast agent. This pattern is defined as an image of a tumor area filled with color in contrast to the surrounding liver. After contrast enhancement, the detectability of a "feeding artery" increased. And also "color filled pattern" appeared in 14 of the 21 hepatocellular carcinomas but none of the nine other liver tumors. In conclusion, contrast enhancement increases the detectability of a "feeding artery" and improves the sensitivity for HCC with color Doppler sonography. A "color-filled pattern" is also effective in the diagnosis of HCC because it requires no technical skill and shows high specificity.

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BACKGROUND AND PURPOSE: The purpose of this study was to assess the ultrasonic imaging of normal rabbit brain by using echocontrast enhancer to identify the brain tissue perfusion. METHODS: A solution of SH/TA-508 (containing microbubbles of mean size 2 to 4 microns; n = 4) was used for contrast enhancement of rabbit brain tissue and was administered through the left internal carotid artery. Contrast enhancement in the ipsilateral parietal area was examined by placing a 7.5-MHz transducer on the dura after a craniectomy. Throughout the experiment, we measured parameters including arterial blood pressure, arterial blood gases, and serum glucose and hematocrit levels. We investigated whether the administration of an echocontrast enhancer would be safe for the brain tissue (n = 4). RESULTS: After injection of 100 mg/mL SH/TA-508, contrast enhancement was clearly observed within approximately 1 second in the left hemisphere (especially in the left cerebral cortex) in all animals and disappeared within 3 seconds after the end of injection. All physiological parameters remained within the normal range throughout the experiment. No focal abnormalities were observed on hematoxylin-eosin staining of the brain tissue. CONCLUSIONS: Contrast enhancement was observed in the ipsilateral hemisphere with the administration of SH/TA-508. Contrast enhancement on B-mode brain imaging would be useful for real-time identification of brain tissue perfusion and should become a promising method for bedside clinical assessment of brain tissue perfusion.

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RATIONALE AND OBJECTIVES: The authors compared the safety and pharmacokinetics of Iotrolan (water-soluble) in hysterosalpingography (HSG) with those of Lipiodol (oil-soluble). METHODS: Iotrolan and Lipiodol were administered intraperitoneally at doses of 100 mg iodine/kg to female rabbits. Retention in the body was investigated by x-ray imaging, plasma kinetics, and urinary and fecal excretion. Irritability in the abdomen was investigated by histologic examination. RESULTS: Iotrolan was entirely excreted into the urine within 2 days after administration. Conversely, Lipiodol was excreted into the urine, had a half-life of 50 days, and was retained for more than 21 days in the abdomen. Iotrolan induced no inflammatory reaction in the abdomen, whereas Lipiodol induced a marked abdominal inflammatory reaction, including granuloma formation. Iotrolan had no effect on iodine concentration in the thyroid; Lipiodol increased iodine concentration significantly. CONCLUSIONS: Iotrolan, which is a water-soluble and nonionic dimeric contrast medium, has potential greater safety for use in HSG than Lipiodol.

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To investigate coupling between the heart and arterial system in patients undergoing elective non-cardiac surgery, we determined both the ventricular elastance and the effective arterial elastance in two groups of subjects: normal group, 68 subjects without heart disease; and cardiac group, 33 subjects with heart disease. Left ventricular end-systolic (Ves) and end-diastolic (Ved) volumes were determined by transesophageal echocardiography. By assuming that left ventricular end-systolic pressure (Pes) is close to mean arterial blood pressure (MAP) and that x-axis intercept (Vo) is zero, the ventricular elastance (E'max) was approximated as MAP/Ves, and the effective arterial elastance (Ea) as MAP/(Ved-Ves). In 222 (74%) of the 299 measurements obtained in normal group, Ea/E'max was nearly 0.5, which is a condition for a maximal mechanical efficiency, while in 61 measurements (20%) Ea was almost equal to E'max (Ea/E'max = 1), which is a condition for maximal stroke work from a given end-diastolic volume. In contrast, in cardiac group, Ea/E'max was nearly 0.5 in 56 (41%) of the 137 measurements, while in 42 measurements (31%) Ea/E'max was nearly 1. In addition, although the value of Ea/E'max over 2, which represents severe heart failure, was not observed in normal group, Ea/E'max was over 2 in 10 measurements (7%) in cardiac group. Thus, the present results suggest that, as reported previously in awake patients, ventriculoarterial coupling is set toward higher left ventricular work efficiency in surgical patients without heart disease, whereas in patients with heart disease, ventricular and arterial properties are so matched as to maximize stroke work at the expense of the work efficiency.

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In the present series of studies we investigated differences in vitro and in animal experiments between iopamidol (Iopamiron, CAS 60166-93-0) and ioversol (CAS 87771-40-2). The studies included the in vitro investigations partition coefficient, lysozyme inhibition, coagulation time and erythrocyte morphology as well as the in vivo paradigms acute toxicity, neural toxicity, general behavior/locomotor activity and angiography. Iopamidol was superior to ioversol in most of the tests. In spite of its higher hydrophilicity, ioversol did not show improved tolerance in comparison to iopamidol.

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Central nervous system (CNS) complications (disturbance of consciousness, focal motor deficits, and seizures) after coronary artery bypass grafting (CABG) and cardiac valve surgery were studied retrospectively. The incidence of CNS complications was significantly more frequent in CABG (11%, 71/638) than in valve surgery (7%, 24/345). Major contributory factors of CNS complications were preexisting cerebrovascular disease and cardiopulmonary bypass time. In comparison to previous reports, older age, hypertension, diabetes mellitus, and cerebrovascular disease were more common in the patients undergoing CABG. The preexisting cerebrovascular disease and prolonged cardiopulmonary bypass time probably increase the risk of cerebral embolism and/or cerebral hypoperfusion. We conclude that patients undergoing CABG surgery are at greater risk for neurological damage in comparison to those undergoing valve surgery.

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Efficacy and tolerability of iotrolan, a nonionic isotonic dimer, as a contrast medium for angiography and urography were investigated in animals. In the arteriography of rabbit femur, the efficacy of iotrolan 280 mgI/ml was as good as iopamidol 300 mgI/ml and better than meglumine diatrizoate 306 mgI/ml. In rat urography, the efficacy of iotrolan 280 mgI/ml was better than both iopamidol 370 mgI/ml and iohexol 350 mgI/ml. Vascular pain was less with iotrolan 280 mgI/ml than with iohexol 300 mgI/ml in rats. Effect of iotrolan on the pulmo-cardiovascular parameters, arterial pO2, hematocrit and plasma osmolality was less than iopamidol and diatrizoate in rabbits. Iotrolan induced no renal dysfunction and diuresis where iopamidol induced diuresis in rats. Effect of iotrolan on the blood coagulation was similar to nonionic monomers and less than diatrizoate in rabbits. Because of its isotonicity, iotrolan induced little water shift in the blood vessel and urinary tract, which would result in good efficacy and tolerability. These results suggest that iotrolan is superior to ionic and nonionic monomers for angiography and urography.

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We studied the usefulness of the pulmonary capillary wedge pressure (PCWP) tracing for the detection of intraoperative myocardial ischemia. Both PCWP wave forms and 7-lead electrocardiogram were monitored in 109 patients undergoing coronary artery bypass graft surgery. Measurements were made six times in each patient. Myocardial ischemia was identified in 99 (27%) of the 366 measurements, and among them, 68 (69%) developed abnormal PCWP wave forms (AC wave greater than 15 mmHg, or V wave greater than 20 mmHg). Although these results were consistent with those of Kaplan et al (1981), we could not agree with their conclusion that PCWP tracing can be helpful in the early diagnosis of subendocardial ischemia. It was not possible to record PCWP continuously because of the risk of pulmonary infarction, and PCWP was influenced by noncardiac factors such as sympathetic reaction to surgical stimuli. We think that PCWP tracing would be of benefit in detecting intraoperative serious ischemia; serious myocardial ischemia was likely to have occurred when abnormalities in both PCWP tracing and ST segment changes were identified. The incidence of both PCWP changes and ECG ischemia was highest in the postbypass period, suggesting that the risk of serious myocardial ischemia is highest in the post-bypass period.

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To examine the relationship between arterial blood pressure and oxygenation in patients undergoing complete surgical correction of tetralogy of Fallot, a retrospective study of 16 patients was first performed, looking at the correlation between mean arterial blood pressure (MAP) and arterial oxygen tension (PaO2). The correlation between phenylephrine-induced changes in MAP (delta MAP) and those in PaO2 (delta PaO2) was investigated prospectively in seven patients. In the retrospective study, there was a significant correlation between MAP and PaO2 (n = 66; r = 0.55; P less than 0.01), and most data points with a PaO2 less than 50 mm Hg were associated with a MAP less than 60 mm Hg. In the seven patients who received phenylephrine, 10 micrograms/kg, a significant correlation was found between delta MAP and delta PaO2 (n = 10; r = 0.95; P less than 0.01). These results suggest that in tetralogy of Fallot arterial blood pressure is a determinant of arterial oxygenation, and that the risk of serious hypoxia is significant when MAP is less than 60 mm Hg.

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Gluconeogenesis was studied in hemoglobin-free perfused livers from chickens that had received daily injections of dexamethasone sulfate for 5 days. Dexamethasone increased to approximately 160% the level of plasma glucose and doubled the content of hepatic glycogen in fed chickens. In the isolated perfused livers from chickens starved for 48 h after the last dexamethasone injection, the rates of production of glucose from lactate decreased by approximately 30% and biphasic changes in glucose production from fructose proceeded in parallel with biphasic changes in the production of lactate and pyruvate. Quinolinate had no effect on gluconeogenesis in both groups. NH4Cl markedly inhibited the production of glucose from pyruvate-lactate mixtures in dexamethasone-treated chickens but stimulated in controls. Aminooxyacetate reversed the effects of NH4Cl in dexamethasone-treated chickens. The data presented provide evidence indicating that the reaction of mitochondrial alanine aminotransferase plays an important role in the regulation of the hepatic gluconeogenesis in dexamethasone-treated chickens.

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1. Starvation for 48 hr doubled the rate of gluconeogenesis from lactate and pyruvate in perfused chicken kidney, but did not change the rate of production of glucose from malate, succinate, or alpha-ketoglutarate. 2. Amino-oxyacetate and D-malate inhibited the production of glucose from lactate and from pyruvate by 55% in each case. Quinolinate reduced the production of glucose from lactate and from pyruvate by 50% in both fed and starved chickens, but had no effect on the production of glucose from intermediates in the citric acid cycle. 3. Starvation increased the rate of formation of mitochondrial phosphoenolpyruvate from pyruvate, but had no effect on the rate of formation of mitochondrial phosphoenolpyruvate from malate.

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