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Biomedical subjects

K D Beller

Publications and source records attributed to K D Beller.

At least 19 recordsLinked to original sources
PubMed1999

Persistent opacification of the left ventricle and myocardium with a new echo contrast agent.

Echo contrast agents with long survival times open up new fields of application in the investigation of tissue perfusion and cardiovascular function. The purpose of this study was to characterize the time-course of the opacification of the heart cavities and myocardium with a new long-lasting second-generation, phospholipid-based echo contrast agent containing perfluoropentane (BY963-C5F12), and to compare its contrast potency with that of air-filled phospholipid monolayer (BY963-air). Doses of 0.03 mL/kg, 0.08 mL/kg and 0.16 mL/kg of BY963-air and BY963-C5F12 were administered intravenously to six conscious dogs weighing 25-36 kg. A transthoracic echocardiography was performed to evaluate peak intensity and area under the curve (AUC) from regions-of-interest placed in the right ventricle, left ventricle and left ventricular (LV) myocardium using acoustic densitometry. All injections were well tolerated, without wall-motion abnormalities or ECG changes. The LV cavity and myocardium were uniformly and well opacified for both echo contrast agents. However, at all administered doses, the contrast efficacy and duration were much more pronounced using BY963-C5F12 than with BY963-air. For the myocardium, the average peak intensity increased from 11.9+/-2.8 to 15.0+/-2.7 (not significant) following injection of BY963-air and from 12.8+/-3.2 to 18.7+/-2.8 (p < 0.01) following IV administration of BY963-C5F12; the latter corresponding to an increase in myocardial opacification of 46%. In conclusion, these results show the high myocardial opacification of BY963-C5F12 as compared to BY963-air. The simple incorporation of a perfluorocarbon gas into the phopholipid monolayer BY963 instead of air alters the acoustic properties of this contrast agent, resulting in qualitatively different application potentials for tissue opacification.

Air↗
PubMed1999

[The effect of carvedilol on contrast echocardiography in comparison to metoprolol in conscious dogs].

This animal study was to demonstrate the effect of the betablockers carvedilol (CAS 72956-09-3) and metoprolol (CAS 37350-58-6), respectively, on myocardial perfusion which was quantified by the use of contrast echocardiography. Each of four experimental schemes were applied consecutively to each of six dogs. They were pretreated with oral administration of either carvedilol (2 mg/kg b. wt.) or with metoprolol (4 mg/kg b. wt.), or received no premedication. 2 h later the contrast agent BY963 (0.03 ml/kg)--a new transpulmonary contrast agent for sonography, based on phopspholipid stabilized microbubbles--was injected intravenously three times at intervals of 2.5 min 5 min in advance and 7.5, 10, 20, and 30 min following the first injection 60 digitized echocardiography images were recorded during a time period of each 2.9 s. From these images average grey-scale values at predetermined points of time were derived. Time-intensity curves of the region of interest of the interventricular septum were computed. Changes in intensity were calculated by baseline subtraction. Myocardial opacification was observed with all injections of the contrast agent in each dog. The effects were marked and no non-responder was observed. There was no return to baseline grey-scale values within the observation period (30 min). Pretreatment with carvedilol was followed by a more pronounced contrast intensity than was with metoprolol. All administrations were well tolerated. No changes in ECG were observed. Heart rate decrease was marked on metoprolol. Blood pressure dropped to a greater extent on carvedilol compared to metoprolol.

Adrenergic beta-Antagonists↗
PubMed1998

The influence of different gases on acoustic properties of a spherosome-based ultrasound contrast agent (BY963). A transcranial Dopplersonography study.

Ultrasound contrast agents improve the signal-to-noise ratio of reflected ultrasound, enhancing the diagnostic value of transcranial Doppler (TCD). In dog studies, we investigated the time course of TCD signal amplitude after application of a phospholipid-containing ultrasound contrast agent (BY963) filled with different gases. The median time of Doppler amplitude enhancement exceeding 5 dB was determined using isoflurane-, isopentane-, trichlortrifluoroethane-, air-, argon-, and perfluoropentane-filled BY963 (69, 72, 75, 78, 88, and 245 seconds respectively). The decrease of time-intensity curve and the duration of signal enhancement showed significant differences comparing the different gases (p = 0.04 and 0.03, respectively). The time course of in vitro stability of BY963 agitated with the different gases measured by absorbance of light (500 nm) showed a retarded decay for perfluoropentane, a rapid decrease for air, isopentane, trichlortrifluoroethane, and argon, and a very rapid decrease using isoflurane. The time course of the different gases depended on the physiochemical properties (lipophilicity and the solubility in water) of the gas encoated in the phospholipid shell. Perfluoropentane-filled BY963 showed the highest in vitro stability and the longest duration of TCD enhancement compared with the other gases used.

Acoustics↗
PubMed1998

Administration of modified spherosome suspension (BY963) leads to an increase of acoustic impedance in dog brain tissue.

Ultrasound contrast agents change the acoustic properties of brain tissue. This can be quantified with acoustic densitometry. In a dog model, the authors examined changes in acoustic impedance in the thalamic and parietal white-matter regions of the brain after intravenous injection of the spherosome containing an ultrasound contrast agent (BY963) filled with perfluoropentane gas. The authors examined six sedated mongrel dogs with a Hewlett-Packard Sonos 1500 device. BY963 filled with perfluoropentane (0.2 ml/kg body weight) was injected three times with a time interval between injections of 5 minutes. Time-dependent changes in mean acoustic impedance were calculated. The authors found a significant increase in peak acoustic impedance after fractional injection of 0.6 ml/kg body weight (3 x 0.2 ml/kg body weight) in the thalamus region up to 7.0 IU (p = 0.006). In the parietal white matter the increase in peak acoustic impedance was not significant (p = 0.06). Statistical comparison of the increase in peak acoustic impedance between placebo and BY963 injection in the thalamus region showed a significant difference after the first injection (p = 0.01) but showed no significance after the second and third injections. The authors concluded that thalamus and parietal white matter of the brain showed different accumulations of BY963.

Animals↗
PubMed1997

Contrast ultrasonography for 2-D opacification of heart cavities, peripheral vessels, kidney and muscle.

Contrast ultrasonography of peripheral vessels and peripheral organs has been only sparsely used to evaluate peripheral tissue blood flow. The purpose of the study was to characterize intraluminal opacification of renal and femoral arteries and veins, of skeletal muscle and renal parenchyma after intraarterial (IA) injection of BY963, a newly developed ultrasound contrast agent being evaluated in Phase II and III trials, and to compare it with opacification of heart cavities after intravenous injection (IV) in dogs. A further purpose was to quantitate possible opacification losses during the first transcapillary passage of BY963 through pulmonary and peripheral microcirculation. BY963 was administered at the dose of 5 mL/animal/vascular territory (0.2 mL/kg). The peak intensity (intensity units = IU) and the area-under-the-curve (AUC, IU x heart cycles) were estimated from regions-of-interest placed in the right ventricle (RV), left ventricle (LV), main renal artery and vein, kidney, femoral artery and vein and adductor muscle. Following single IV injection, the average peak intensity and AUC values were 33 +/- 3 (mean +/- SE) and 674 +/- 109 for the RV, and 27 +/- 2 and 870 +/- 74 for the LV (p < 0.05), respectively. Following single IA injection in the descending aorta, the average peak intensities and AUC values were 35 +/- 2 and 613 +/- 139 in the renal artery and 26 +/- 4 (p < 0.05) and 639 +/- 151 in the renal vein (nonsignificant), respectively. For the femoral vessels, the average peak intensities and AUC values were 30 +/- 3 and 469 +/- 63 in the femoral artery, and 21 +/- 2 (p < 0.05) and 517 +/- 44 in the femoral vein (nonsignificant), respectively. The values for the output-to-input intensity ratios for peak intensity and AUC were 0.82 +/- 0.06 and 1.36 +/- 0.12 for the LV/RV ratio, 0.73 +/- 0.08 and 1.02 +/- 0.05 for the renal vein/renal artery ratio, and 0.71 +/- 0.09 and 1.16 +/- 0.13 for the femoral vein/femoral artery ratio, respectively (nonsignificant). In conclusion, these results demonstrate the high opacification potency of BY963 in the LV, renal and femoral veins, being of the same order of magnitude as that in the RV, renal and femoral arteries, respectively. Finally, the loss of opacification properties of BY963 during the first transcapillary (pulmonary or peripheral-capillary) passage is minimal.

Animals↗
PubMed1997

Transcranial Doppler echo contrast studies using different colour processing modes.

OBJECTIVES: To study the effects of different colour imaging modes on the contrast-medium-enhanced image of the intracranial cerebral arteries. METHODS: Twelve healthy volunteers were studied transcranially after administration of 10 ml BY963 successively with Power Doppler (p-TCCS) and with colour Doppler frequency imaging mode (f-TCCS) in a randomized order. RESULTS: The latency time (mean+/-SD) from the injection until the signal enhancement in the middle cerebral artery was 17.1+/-5.8 s for p-TCCS and 17.8+/-4 s for f-TCCS, and the duration of the optimal diagnostically useful signal enhancement was 44.2+/-8.2 s and 40.2+/-12.6 s respectively. CONCLUSIONS: Based on the measured parameters, both imaging modes were of equal value. Theoretical differences in sensitivity of the two methods play no particular role facing the immense signal enhancement after echo contrast application.

Adult↗
PubMed1997

Characteristics of transcranial Doppler signal enhancement using a phospholipid-containing echocontrast agent.

BACKGROUND AND PURPOSE: Ultrasound attenuation caused by the skull is a major limitation of transcranial Doppler. Echocontrast agents (EAs) may solve this problem. The aim of the present study was to investigate the characteristics of a new echocontrast agent (BY963) containing air bubbles stabilized by phospholipids. METHODS: Nine healthy volunteers received three different doses (2.5, 5.0, and 10 mL) of BY963 at an injection rate of 0.25 mL/s. The Doppler signal amplitude obtained from the middle cerebral artery was recorded with a 2-MHz pulsed-wave Doppler system. After complete decay of the signal enhancement, upward stroking of the veins of the upper arm was performed to evaluate the stability of the EA in the venous system. RESULTS: A dose-dependent increase of at least 30 dB in the Doppler signal amplitude lasted 19 to 47, 35 to 64, and 48 to 126 heart cycles (68% range) after 2.5, 5.0, and 10 mL EA, respectively. In 6 cases, there was a biphasic increase in EA enhancement. Upward stroking of the forearm, in general 12 to 18 minutes after administration, caused a Doppler signal enhancement of at least 30 dB in 6 cases. CONCLUSIONS: Each injection of BY963 caused a diagnostically relevant Doppler signal enhancement. A considerable amount of EA remained stable in the venous system for at least 12 minutes. The biphasic dose-response fits to models of dilution-indicator theory and indicates free recirculation, as well as a nonlinear washout curve.

Adult↗
PubMed1996

Pharmacokinetic studies of different echo-contrast agents in the cerebral circulation of dogs.

Ultrasound contrast agents (UCAs) are improving the signal-to-noise ratio of the reflected ultrasound so that Doppler frequency spectra can be recorded even under poor sonographic conditions. This is of particular diagnostic value in transcranial Doppler sonography. Depending on specific pharmacologic properties, echo-contrast agents may cause different increase and duration in Doppler signal amplitude. We used a dog model to study the temporal profile of Doppler signal amplitude after application of a phospholipid-containing echo-contrast agent (BY 963). In addition, we compared it with a contrast agent containing albumin (Albunex). Spherosome suspension BY 963 resulted in a dose-dependent increase in the duration of ultrasound amplification (Doppler enhancement of 1 mL, 3 mL and 10 mL of BY 963 per animal: 62.4 +/- 8.4, 72.8 +/- 9.2 and 67.7 +/- 4.2 s, respectively, n = 6). Detection of BY 963 in the extracranial jugular vein demonstrated that the UCA passes through the cerebral microcirculation (cerebral transit time was 2.2 +/- 0.2 s, n = 4). The signal enhancement lasted longer using the spherosome suspension compared with the albumin-containing solution (77.2 +/- 11.6 and 31.1 +/- 3.7 s, respectively, n = 6), and the maximum increase in intensity was more pronounced (27.0 +/- 2.0 and 17.5 +/- 2.2 dB, respectively, n = 6).

Albumins↗
PubMed1996

[Duplex ultrasound with echo contrast media].

Intravenous echo contrast agents transversing the lungs lead to improved detection of blood flow in arteries and veins due to enhancement of the Doppler signal by 20-25 dB. This echo enhancement improves the visualisation of vessel sections that are otherwise difficult to examine due to obesity, to deep vessel location, scarring or low flow state. The available contrast agents that pass through the lungs and are used in controlled studies, possess similar physico-chemical properties: mean bubble diameter 2-4 microns, viscosity and pH value close to that of the blood. The contrast agents enable the plotting of densitometric wash-in and wash-out curves from the heart and the vessels to aid in the investigation of tissue perfusion. Echo contrast agents induce some technical side effects that must be known to avoid annoying diagnostic pitfalls: spectral bubble noise, colour blooming, acoustic shadowing and changes in Doppler frequency shifts. Their origin and measures to avoid them are discussed. The contrast agents that pass through the lungs open up new fields of application in the investigation of blood flow.

Artifacts↗
PubMed1995

Phase I: transcranial echo contrast studies in healthy volunteers.

BACKGROUND AND PURPOSE: Transcranial ultrasound diagnostics are particularly hindered by insufficient ultrasound penetration through the temporal bone. The use of ultrasonic contrast media to enhance the Doppler signal is an important step toward the solution of this problem. In the present study we investigated the tolerability and the diagnostic value of a new intravenous transpulmonary ultrasonic contrast medium, BY963. METHODS: In two phase I studies, 8 healthy volunteers received a spherosome suspension containing a phospholipid as the active ingredient. The intravenous injection was performed in three doses (2.5, 5, and 10 mL) at four different injection rates (0.25, 0.5, and 1 mL/s and bolus). The duration and degree of the signal enhancement were measured by two transcranial ultrasonic procedures presently used in clinical practice: transcranial Doppler sonography (TCD) and transcranial color-coded sonography (TCCS). The assessment of tolerability was based on chemical laboratory parameters and hemodynamic data (heart rate, blood pressure, electrocardiogram) and on questionnaires relating to general well-being. RESULTS: BY963 was tolerated without complications. All 38 administrations of the echo contrast medium produced a marked increase in the TCD signal (> 30 dB) in the intracranial basal cerebral arteries. To obtain the optimum time window for diagnostic use, higher doses with slower injection rates are advantageous. The duration of optimal contrasting was 42 to 68 seconds (TCD) and 12 to 132 seconds (TCCS), depending on the method and mode of administration. Bolus injections gave rise to an increased incidence of color artifacts. CONCLUSIONS: BY963 significantly improves intracranial Doppler imaging while being well tolerated. The signal enhancement lasts long enough for TCCS to display all basal cerebral arteries after just one injection.

Adult↗
PubMed1995

Influence of sonographic contrast media on microcirculation in rats.

In an open placebo-controlled study the influence of the injection of different sonographic contrast media on the microcirculation was proved. The study was performed in 7 Sprague-Dawley rats. In order to examine this query two different sonographic contrast media in comparison to agitated electrolyte solution (as the placebo) were injected into the abdominal aorta of 7 anaesthetized rats as a 2 ml/kg bolus at 10-min intervals. Examined were a newly developed agitated ultrasound solution (AK I: an aequeous solution of a vegetable phospholipid) and a radiographic contrast agent (AK II: 741 mg Ioversol or 350 mg iodine, respectively, per ml) which is used in an agitated form as ultrasound contrast agent, too. 1 min before and until 2 min after each injection the capillary perfusion of the same vessel area in the major omentum was measured (video-recording by use of intravital microscopy). The erythrocyte velocity was determined off-line by an image analysing system. Whereas the agitated X-ray contrast medium AK II decreases the mean capillary perfusion (temporary flow stagnation in single capillaries), AK I as well as agitated electrolyte solution did not influence the capillary erythrocyte velocity in the major omentum. The gaps which appeared immediately after the injection of AK I seem to have been brought about by spherosomes of AK I. Still the spherosomes are so small that they can pass through the capillaries, or if they are larger which cannot be determined using in vivo microscopy the flow force necessary for the deformation of the bubbles is so small that the capillary perfusion is not influenced. The injection of agitated AK I does not lead to significant changes of the microcirculation.

Animals↗
PubMed1990

Involvement of 5-HT1A receptors in blood pressure reduction by 8-OH-DPAT and urapidil in cats.

This study investigated the effects of (-)-pindolol, a putative 5-HT1A receptor antagonist, upon the central hypotensive action of the antihypertensive drug urapidil and of the purported 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in cats. Chloralose/urethane-anesthetized cats were thoracotomized and artificially ventilated. Blood pressure was monitored in the iliac artery, and the drugs were injected into the vertebral artery. Urapidil (1-300 nmol/kg) or 8-OH-DPAT (0.01-1 nmol/kg) dose-dependently reduced blood pressure. (-)-Pindolol (30 and 100 nmol/kg) shifted the dose-response curves of both drugs significantly and in a similar manner to the right. Doses of urapidil of 30 nmol/kg or higher also reduced the elevation of blood pressure following the intravenous injection of the alpha 1-adrenoceptor agonist cirazoline whereas 8-OH-DPAT was ineffective. Yet, the hypotensive response to the directly acting vasodilator nitroglycerin remained unchanged after urapidil. The results support the hypothesis that the centrally mediated component of the antihypertensive action of urapidil is due to stimulation of 5-HT1A receptors in the brainstem. Peripheral alpha 1-adrenoceptor blockade comes into play with higher doses of the drug administered via the vertebral artery.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Involvement of brain 5-HT1A receptors in the hypotensive response to urapidil.

Stimulation of serotonin-1A (5-hydroxytryptamine) (5-HT1A) receptors in the brain stem has been suggested to contribute to the antihypertensive action of the alpha 1-adrenoceptor antagonist urapidil. This hypothesis was tested by analyzing the influence of the 5-HT1A receptor antagonist spiroxatrine on the hypotensive responses to urapidil and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Chloralose/urethane-anesthetized cats underwent thoracotomy and were artificially ventilated. Blood pressure was monitored in the femoral artery. Urapidil (0.01 to 10 mumol/kg) or 8-OH-DPAT (3 to 30 nmol/kg) was injected into a femoral vein and the maximal hypotensive response recorded. A dose-response test with both drugs was performed before and after administration of spiroxatrine (3 and 10 nmol/kg); the latter was given through the vertebral artery, thus delivering the antagonist to the brain stem. Blood pressure was dose-dependently reduced by urapidil and 8-OH-DPAT after intravenous injection. Central administration of spiroxatrine through the vertebral artery shifted the dose-response curves of both drugs markedly and in a dose-dependent manner to the right, while the hypotensive response to the peripheral vasodilator nitroglycerin remained unchanged. The results suggest that the hypotensive response after peripheral administration of urapidil is mediated in part by stimulation of brain 5-HT1A receptors and this effect on central cardiovascular regulation is additive to the blood pressure reduction resulting from peripheral alpha-adrenoceptor blockade.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Evidence for the interaction of urapidil with 5-HT1A receptors in the brain leading to a decrease in blood pressure.

Current knowledge about the role of serotonin (5-HT) in central cardiovascular regulation is reviewed. Results from experiments with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) suggest that activation of somatodendritic 5-HT1A receptors in the medulla oblongata decreases the firing of serotoninergic neurons and thus reduces their excitatory input to the sympathetic neurons in the intermediolateral cell column. As a consequence, blood pressure is reduced by 5-HT1A receptor agonists. Urapidil is an antihypertensive drug that has a dual mode of action: peripheral alpha-adrenoceptor antagonism and interaction with 5-HT1A receptors in the brain. This profile can adequately explain the vasodilation and lack of significant sympathetic activation observed during urapidil treatment.

Animals↗
PubMed1988

Interaction of urapidil with brain serotonin-1A receptors increases the blood pressure reduction due to peripheral alpha-adrenoceptor inhibition.

The alpha-adrenoceptor antagonist urapidil influences central cardiovascular regulation, and this effect is unrelated to alpha-adrenoceptors. Since urapidil has appreciable affinity and selectivity for serotonin-1A (5HT1A) receptors, the activity of urapidil at these sites may be relevant for the centrally mediated component of its antihypertensive action. The latter hypothesis was tested by analysing the influence of the 5HT1A receptor antagonist spiroxatrine on the hypotensive response to urapidil, in comparison with the influence on the hypotensive response to the 5HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin). Anaesthetized cats were thoracotomized and artificially ventilated. Blood pressure was monitored in the descending aorta, and the drugs were injected into the vertebral artery. Spiroxatrine (0.1-3.0 nmol/kg) shifted the cumulative dose response curve (blood pressure reduction) of urapidil (3-20 nmol/kg) and of 8-OH-DPAT (0.01-0.1 nmol/kg) to the right, suggesting competitive antagonism. The results support the hypothesis that the effects of urapidil on central cardiovascular regulation and at least part of the hypotensive effects are due to 5HT1A receptor stimulation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗