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Biomedical subjects

M W Keller

Publications and source records attributed to M W Keller.

At least 19 recordsLinked to original sources
PubMed1997

Arteriolar constriction in skeletal muscle during vascular stunning: role of mast cells.

Striated muscle becomes stunned during reperfusion after sublethal ischemia. Resistance vessel tone and reactivity are altered in stunned muscle tissues. The hypothesis that adenosine-regulated mast cell degranulation occurs during reperfusion and leads to constriction of resistance arterioles was tested. The hamster cremaster muscle was subjected to 1 h of ischemia followed by reperfusion. Resistance arterioles constricted during reperfusion (74% of maximal diameter at baseline vs. 42% of maximal diameter after 30 min of reperfusion; P < 0.01). Mast cells degranulated in reperfusion concomitant with arteriolar constriction. Stimulation of mast cell degranulation in control animals with compound 48/80 or cold superfusate (21 degrees C) caused vasoconstriction that mimicked that seen in reperfusion. The mast cell stabilizer cromolyn blocked degranulation and constriction. If mast cell granules were depleted by applying compound 48/80 before inducing ischemia, then arterioles failed to constrict during reperfusion. Adenosine A3-antagonist BW-A1433 abolished constriction. These findings suggest that arterioles constrict in reperfusion due to adenosine-regulated mast cell degranulation. Vasodilation in response to sodium nitroprusside and acetylcholine was normal in stunned, constricted arterioles. However, the dose-response curves to adenosine were shifted to the left in arterioles constricted by either stunning, compound 48/80, exposure to cold superfusate, or cromolyn compared with control vessels. Depletion of granular components via stunning, compound 48/80, cold superfusate, or inhibition of secretion with cromolyn results in unopposed A1- or A2-mediated vasodilation in response to adenosine, whereas the dilatory effects of adenosine are blunted by simultaneous release of vasoconstrictors from mast cells in control animals. In summary, it was found that mast cell degranulation occurs during reperfusion and leads to constriction of resistance arterioles and altered vascular reactivity to adenosine. Adenosine is released in ischemia and stimulates mast cell degranulation via the A3 receptor located on mast cells during reperfusion.

Acetylcholine↗
PubMed1994

Determination of capillary tube hematocrit during arteriolar microperfusion.

Intracapillary hematocrit is known to be substantially lower than arterial hematocrit. We hypothesized that capillary hematocrit might be influenced by interactions between plasma macromolecules and the endothelial cell surface. Microvessel perfusion pipettes were inserted in second- or third-order vessels, and capillaries were perfused with three different artificial bloods composed of 50% red cells plus the following suspension media: fetal calf serum (group I), serum albumin plus serum globulins (fractions II and III; group II), and bovine serum albumin plus dextran (group III). The mean hematocrits of the pipette-perfused capillaries averaged close to 50% of the systemic value with all perfusion fluids and were not different from the hematocrits of the capillaries perfused by the animal. These data suggest that bifurcations proximal to the pipette location did not contribute to the reduction in mean tube hematocrit normally seen in the animal. Furthermore, interactions between the plasma macromolecules and the endothelial cell surface do not appear to contribute to the low intracapillary hematocrit. Analysis of the data indicate that the capillary Fåhraeus effect, the network Fåhraeus effect in terminal vessels of the arterial tree, and intracapillary events all contribute to the reduction in intracapillary hematocrit.

Adenosine↗
PubMed1994

Time course of coronary endothelial healing after injury due to ischemia and reperfusion.

BACKGROUND: Although it has been demonstrated in short-term preparations that ischemia with early reperfusion results in coronary vascular injury manifested by abnormal endothelium-dependent relaxation and increased permeability to plasma proteins, it has not been clear whether these abnormalities are permanent or reversible. METHODS AND RESULTS: In a canine model, regional coronary ischemia was accomplished by 1 hour of left anterior descending coronary artery ligation, and follow-up studies were performed after reperfusion for 1 hour, 48 hours, 2 weeks, or 9 weeks. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilator ADP and the endothelium-independent vasodilator nitroprusside. At 1 and 48 hours of reperfusion, relaxation of rings from the ischemic reperfused artery to ADP was blunted, but relaxation to nitroprusside was normal. At 2 weeks there was a nonsignificant trend toward a blunted response to ADP in the ischemic/reperfused rings, and at 9 weeks a completely normal response to ADP was observed. Coronary microvascular permeability was assessed by measurement of protein leak index (PLI), by using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. At 1 and 48 hours of reperfusion there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. There was a small increase in PLI at 2 weeks but a completely normal measurement at 9 weeks. Electron microscopy of ischemic/reperfused vessels demonstrated endothelial cell swelling and other abnormalities in epicardial arteries and the microcirculation at 48 hours of reperfusion but normal endothelium at 2 weeks of reperfusion. CONCLUSIONS: After 1 hour of regional coronary ischemia, coronary endothelial injury occurs early in reperfusion with abnormalities in epicardial coronary artery endothelium-dependent relaxation, coronary microvascular permeability, and both epicardial coronary artery and microvascular histology. This pattern of injury persists for at least 48 hours, but there is partial functional and complete histological recovery within 2 weeks and complete functional recovery within 9 weeks.

Animals↗
PubMed1991

Importance of two-dimensional echocardiographic assessment of left ventricular systolic function in patients presenting to the emergency room with cardiac-related symptoms.

BACKGROUND: This prospective study was designed to test the hypothesis that the assessment of left ventricular systolic function at the time of emergency room (ER) presentation provides valuable diagnostic and prognostic information in patients with cardiac-related symptoms. METHODS AND RESULTS: The study is based on a 2-year follow-up of 171 consecutive patients evaluated in the ER for such symptoms. In the course of follow-up, one third of the patients (55 of 171) suffered a major cardiac event. For those with left ventricular systolic dysfunction (LVSD), the age-adjusted rate of early events (occurring within 48 hours of presentation) was more than eight times higher than for those without LVSD (26.9% versus 3.3%, p less than 0.01). For events occurring after 48 hours of ER presentation, LVSD was associated with a nearly fourfold excess of cardiac events (23.9% versus 6.4%, p less than 0.01). Other than advanced age, the most important confounder for early events included an abnormal electrocardiogram diagnostic for acute myocardial infarction. Confounders for late events included advanced age and a history of hypertension. LVSD on two-dimensional echocardiography (2DE) was the only finding associated with early and late events after controlling for other risk factors. In addition, the prediction of these events derived from the combination of historical, clinical, electrocardiographic, and 2DE findings was significantly improved when accounting for the presence or absence of LVSD (p less than 0.01). CONCLUSIONS: We conclude that the 2DE assessment of left ventricular systolic function provides valuable diagnostic and prognostic information in subjects presenting to the ER with cardiac-related symptoms.

Angina Pectoris↗
PubMed1991

Microcirculatory dysfunction following perfusion with hyperkalemic, hypothermic, cardioplegic solutions and blood reperfusion. Effects of adenosine.

BACKGROUND: Cardioplegic solutions have been used to enhance myocardial preservation during cardiac surgery. The benefits derived from preventing myocardial ischemia with cardioplegic solutions may, however, be countered by tissue damage that occurs when the myocardium is reperfused with oxygenated blood. Furthermore, cardioplegia-induced endothelial dysfunction may contribute to depressed myocardial function postoperatively. The endothelium of coronary arteries and vein grafts is damaged by crystalloid cardioplegic solutions. There is less known about the effects of cardioplegic solutions on the microvasculature. METHODS AND RESULTS: The hypothesis that microvascular damage occurs following perfusion with hyperkalemic, crystalloid, cardioplegic solutions and blood reperfusion, leading to decreased blood flow and increased neutrophil accumulation, was tested in a model system. Intravital microscopic observations were performed during a 20-minute perfusion of the hamster cremaster muscle with cardioplegic solutions (10 degrees C) via the femoral artery with the iliac occluded and during a subsequent 2-hour blood reperfusion period (iliac open). Arteriolar vasoconstriction (27% decrease in diameter, p less than 0.05) and a 25% decrease in the density of perfused capillaries (p less than 0.05) occurred during reperfusion in hamsters receiving crystalloid cardioplegic solution (16 meq K+) compared to control hamsters (no cardioplegic solution given). Neutrophils accumulated on venular endothelium in treated animals (250% increase, p less than 0.05) and extravascularly (myeloperoxidase levels 2.0 +/- 0.4 U/g versus 1.3 +/- 0.3 U/g in control, p less than 0.05). The addition of adenosine (10(-4) M) and albumin (2 g%) to the cardioplegic perfusate, accompanied by the administration of adenosine (10(-4) M) during reperfusion, produced arteriolar vasodilation (34% diameter increase, p less than 0.05) and inhibited extravascular neutrophil accumulation (myeloperoxidase level of 1.5 +/- 0.2 U/g, p greater than 0.05 versus control). Capillary perfusion, however, was still significantly diminished (28% decrease, p less than 0.05.) CONCLUSIONS: We conclude that injury manifest by decreased microvascular blood flow and increased neutrophil accumulation in tissues occurs after perfusion with hypothermic, hyperkalemic, crystalloid cardioplegic solutions and blood reperfusion. Adenosine seems to partially attenuate this injury by dilating arterioles and decreasing extravascular neutrophil accumulation.

Adenosine↗
PubMed1991

Value of regional wall motion abnormality in the emergency room diagnosis of acute myocardial infarction. A prospective study using two-dimensional echocardiography.

Because regional wall motion abnormality (RWMA) is usually noted during ischemia, we hypothesized that the presence of this finding with two-dimensional echocardiography would be superior to conventional methods of diagnosing acute myocardial infarction (AMI) in the emergency room. We also hypothesized that because the absence of RWMA would probably not be associated with AMI, the use of two-dimensional echocardiography would significantly limit unnecessary hospital admissions. To test these hypotheses, we undertook a prospective study that used two-dimensional echocardiography in 180 patients presenting to the emergency room with symptoms suggestive of AMI. The emergency room physicians were not informed of the two-dimensional echocardiography findings, and their decision to admit or not admit to the hospital was based on conventional clinical and electrocardiographic criteria. Forty patients were not admitted to the hospital and 140 were admitted. Of the 30 patients with enzyme-confirmed AMI, nine had typical ST elevation on the ECG that was consistent with acute injury, three had normal ECGs, and eight had ECGs in the presence of which AMI could not have been diagnosed (left bundle branch block, paced rhythm, or repolarization changes); the rest had nonspecific ECG findings. Of the 29 AMI patients with technically adequate two-dimensional echocardiography studies, two did not demonstrate RWMA and 27 had RWMA, compared with nine with diagnostic ECG changes (p less than 0.001). Of the 13 patients with in-hospital complications only four had an initial ECG showing ST elevation, and all 13 had RWMA (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Intraoperative assessment of regional myocardial perfusion using quantitative myocardial contrast echocardiography: an experimental evaluation.

To test the hypothesis that myocardial contrast echocardiography can be used to quantitate regional myocardial flow in the arrested heart at the time of delivery of cardioplegic solution, data were acquired in 13 dogs on cardiopulmonary bypass. Different degrees of stenosis were placed in random order on the left anterior descending coronary artery. For each stenosis, myocardial contrast echocardiography was performed by injecting sonicated albumin microbubbles into the cross-clamped aortic root at the time of delivery of cardioplegic solution. The resultant echocardiographic images were analyzed on an off-line computer. Background-subtracted time-intensity plots were generated, and an exponential function, f(t) = Ce-alpha t + De- beta t, was applied to each plot. Variables that reflected the total number of microbubbles entering the coronary artery bed, such as the area under the curve and the peak height of the curve, correlated best with radiolabeled microsphere-measured myocardial flow (r = 0.92 and r = 0.91, respectively). Variables that reflected the appearance of contrast microbubbles in the myocardium, such as the initial slope and the slope at 1 s, also had a good correlation with myocardial flow (r = 0.84 and r = 0.89, respectively). Variables that reflected the washout of contrast medium from the myocardium, such as the slope of the descending portion of the curve, had only a fair correlation with myocardial flow (r = 0.65). In six dogs, the technique of injecting contrast medium into the cross-clamped aortic root was also examined. Although continuous infusion of contrast medium produced smaller perturbations in mean aortic and distal left anterior descending artery pressures compared with a bolus injection (p less than 0.01), the correlation between the variables of the time-intensity curves and flow was equally close with both techniques. It is concluded that it is possible to quantitate myocardial flow by using myocardial contrast echocardiography at the time of delivery of cardioplegic solution in dogs on cardiopulmonary bypass. The implementation of this technique in humans might be useful in guiding the sequence of graft placement and thereby improving myocardial preservation during coronary artery bypass operations.

Animals↗
PubMed1989

Assessment of regional myocardial blood flow with myocardial contrast two-dimensional echocardiography.

It was hypothesized that regional myocardial blood flow could be measured using myocardial contrast echocardiography. Accordingly, arterial blood was perfused into the coronary circulation in 16 dogs. In Group 1 dogs (n = 8), blood flow to the cannulated left circumflex artery was controlled with use of a roller pump, whereas in Group 2 dogs (n = 8) blood flow to the left anterior descending coronary artery was controlled by a hydraulic occluder placed around it. Sonicated microbubbles (mean size 4 microns) were used as the contrast agent. In Group 1 dogs the microbubbles were injected subselectively into the left circumflex artery, whereas in Group 2 dogs they were injected selectively into the left main coronary artery and two-dimensional echocardiographic images were recorded. Computer-generated time-intensity curves were derived from these images and variables of these curves correlated with transmural blood flow measured with radiolabeled microspheres. A gamma-variate function (y = Ate-alpha t) best described the curves, and alpha (a variable of curve width) correlated well with transmural blood flow at different flow rates in all Group 1 and Group 2 dogs (mean r = 0.81 and 0.97, respectively). Other variables of the curve width also correlated well with myocardial blood flow, but peak intensity had a poor correlation with myocardial blood flow in both groups of dogs (r = 0.39 and r = 0.63, respectively). When data from all dogs were pooled, Group 1 dogs still showed good correlation between variables of curve width and myocardial blood flow (r = 0.81); Group 2 dogs did not (r = 0.45). The difference between the two sets of dogs was related to the site of contrast agent injection. It is concluded that measurement of the transit time of microbubbles through the myocardium with two-dimensional echocardiography accurately reflects regional myocardial blood flow. Although injection of contrast agent selectively into the left main coronary artery only allows measurement of relative flow, it may be feasible to measure absolute flow by injecting contrast agent subselectively into a coronary artery. Myocardial contrast echocardiography may, therefore, offer the unique opportunity of simultaneously assessing regional myocardial perfusion and function in vivo.

Animals↗
PubMed1989

The behavior of sonicated albumin microbubbles within the microcirculation: a basis for their use during myocardial contrast echocardiography.

The purpose of this study was to determine whether the behavior of sonicated albumin microbubbles accurately mimics red blood cell flow in the microcirculation and is thus consistent with their use as in vivo tracers of red blood cell flow during myocardial contrast echocardiography. Accordingly, microbubbles prepared from fluorescein-conjugated albumin and fluorescently labeled red blood cells were injected intravascularly in eight golden hamsters. Their intravascular distribution, velocities, arteriolar-to-venular transit and flux ratios at branch points were determined in the microcirculation of the cheek pouch. Albumin microbubbles (mean diameter, 4.9 +/- 3.6 microns) and red blood cells displayed a similar frequency of distribution across the arteriolar lumen (33% in the central 20% of the arterioles), and their arteriolar velocities were also similar (2.5 +/- 0.7 mm/sec and 2.3 +/- 0.7 mm/sec,p = NS). The mean velocities of microbubbles correlated well with those of red blood cells at baseline and after adenosine application (r = 0.97 and r = 0.89, respectively), as did the calculated maximum velocity (r = 0.98 and r = 0.80, baseline and adenosine, respectively). The velocity profiles across the lumen of the vessels for albumin microbubbles and red blood cells were similar at baseline and after adenosine-induced velocity changes. The flux ratios at branch points also correlated well (r = 0.92, p less than 0.001). Arteriolar-to-venular transit times of albumin microbubbles were similar to those of red blood cells in vessels ranging in size from 22 microns to 45 microns. We conclude that the behavior of albumin microbubbles in the microcirculation mimics that of red blood cells and supports their use as intravascular tracers of red blood cell flow during myocardial contrast echocardiography.

Animals↗
PubMed1988

Success of internal mammary bypass grafting can be assessed intraoperatively using myocardial contrast echocardiography.

To determine whether the success of internal mammary artery bypass grafting can be assessed intraoperatively using myocardial contrast echocardiography, sonicated Renografin-76 was injected into the aortic root of 11 dogs during the delivery of cardioplegic solution. Studies were performed with the left anterior descending coronary artery patent and totally occluded, and after internal mammary artery bypass grafting distal to the occluded vessel. Flow rate during cardioplegia was constant for all three stages in each experiment. Myocardial contrast echocardiography clearly demonstrated homogeneous myocardial perfusion with the left anterior descending coronary artery patent, lack of perfusion in the left anterior descending artery bed during its occlusion and excellent perfusion of the occluded bed after internal mammary artery bypass grafting distal to the occlusion in 10 of the 11 dogs. In one dog, the bypass graft was technically inadequate and contrast opacification was not noted in the left anterior descending artery bed after internal mammary artery bypass grafting. The exponential function C(t) = Ae-alpha t + Be-beta t was fitted to computer-derived time-intensity curves from the myocardium, where alpha denotes contrast washout and beta denotes contrast appearance. Respective values for alpha and beta (mean + 1 SD) were similar for the patent left anterior descending coronary artery and after internal mammary artery bypass grafting distal to the occluded artery (0.11 +/- 0.10 versus 0.10 +/- 0.10, and 2.5 +/- 2.4 versus 1.1 +/- 0.56). In conclusion, myocardial contrast echocardiography has potential for intraoperative assessment of the adequacy of coronary artery bypass grafting.

Animals↗
PubMed1988

Myocardial contrast echocardiography in humans. II. Assessment of coronary blood flow reserve.

The hypothesis that myocardial contrast echocardiography could be used to simultaneously assess coronary blood flow reserve and the size of the perfusion bed supplied by a coronary artery was examined in nine patients and six dogs. All patients were undergoing cardiac catheterization and had single vessel coronary artery disease (greater than or equal to 85% stenosis of either the proximal left anterior descending or the left circumflex coronary artery); the six dogs had a critical stenosis of the left circumflex coronary artery. Three milliliters of sonicated Renografin-76 (mean microbubble size 6 micron) was injected into the left main coronary artery before and after intracoronary administration of papavarine, 6 to 9 mg. The beds supplied by the normal and stenotic vessels could not be differentiated during contrast echocardiography before injection of papavarine. However, after papavarine, the normal vascular bed showed significantly more contrast enhancement than did the bed supplied by the stenotic artery. This disparity in contrast enhancement made it possible to delineate the size of the bed perfused by the stenotic vessels. When quantitative analysis of the time-intensity curves obtained from the echocardiograms was performed in the dogs, the absolute values for the area under the curve, peak contrast intensity and curve width did not correlate with absolute blood flows measured with radiolabeled microspheres. However, the ratios of the areas under the curves derived from the two vascular beds before and after papavarine correlated well with the ratios of blood flows between the two beds during the same stages (r2 = 0.73 by linear regression and r2 = 0.85 by an exponential function). In comparison, the ratios of peak amplitudes and curve widths before and after papavarine had poor correlations with ratios of flows from the two beds (r2 = 0.18 and 0.02, respectively). In conclusion, myocardial contrast echocardiography can be used to simultaneously assess coronary blood flow reserve and the size of the perfusion bed supplied by a stenotic vessel.

Aged↗
PubMed1988

Myocardial contrast echocardiography without significant hemodynamic effects or reactive hyperemia: a major advantage in the imaging of regional myocardial perfusion.

All agents used for myocardial contrast echocardiography to date produce adverse hemodynamic effects and alter coronary blood flow. It was hypothesized that because 5% human albumin, when sonicated for use as a contrast agent, is neither hyperosmolar nor a calcium chelator, it would not have significant effects on coronary blood flow, left ventricular function or systemic hemodynamics. Albumin microbubbles of two distinct sizes (mean size 2.9 and 5.8 micron) were produced and compared with nonsonicated albumin, nonsonicated Renografin, sonicated Renografin and hand-agitated Renografin for their effects on hemodynamics, coronary blood flow and regional left ventricular systolic thickening in 15 open chest anesthetized dogs. None of the albumin solutions significantly altered left atrial, left ventricular systolic and end-diastolic and mean aortic pressures. These agents did not cause a coronary hyperemic response or alter left ventricular systolic thickening, but slightly lowered the peak positive left ventricular maximal rate of rise in pressure (dP/dt) (-4.1 +/- 5.4%, p less than 0.01). In contrast, all the Renografin solutions caused significant changes in all these variables (p less than 0.02). In six dogs. albumin solutions did not alter these variables even in the presence of critical coronary stenosis. The contrast opacification produced by 5.8 micron albumin microbubbles was equivalent to that produced by sonicated Renografin. Compared with an equivalent amount of saline and nonsonicated albumin solutions, 10 ml of sonicated albumin did not produce any evidence of infarction, embolization or hemorrhage in the myocardium, brain or kidneys of rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Successful left ventricular opacification following peripheral venous injection of sonicated contrast agent: an experimental evaluation.

A new agent for use in contrast echocardiography that is capable of passing through the pulmonary circulation and opacifying the left ventricular cavity after intravenous injection was evaluated in a canine model. Air-filled albumin microbubbles were produced by sonication. A Coulter counter was used to size and count the resultant microbubbles in vitro. The microbubbles had diameters sufficiently small (less than 9 micron) to permit transpulmonary passage. A total of 72 injections were made into the forepaw vein of five closed-chest dogs. Simultaneous two-dimensional echocardiographic images of the right ventricle and the left ventricle were recorded and digitized on an off-line computer. Of the 72 injections, 59 (82%) were suitable for digitization. Forty of the 59 digitized injections (68%) demonstrated left ventricular contrast enhancement. Indicator-dilution curves were generated from plots of intraventricular gray level VS time, and the curve widths and areas under the curves were determined. The ratio of total indicator curve area for left to right ventricular cavity was 0.39 for the 40 successful injections, indicating transpulmonary transmission of 39% of the contrast effect. Injection of bubbles with mean size less than 6 microns resulted in a larger median left ventricular curve area than those with bubbles averaging from 6 to 9 microns. Injections demonstrating successful left ventricular contrast opacification had larger right ventricular curve areas than those that were not successful. Blood pressure, heart rate, and arterial blood gases were not significantly altered by repeated intravascular contrast injections. Postmortem examination of hearts, lungs, livers, and kidneys revealed no histologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

An innovative approach to assessing outcome of long-term psychiatric hospitalization.

The failure of research on long-term hospital treatment to show consistent relationships between length of stay and treatment outcome may reflect a need for more refined measures to evaluate long-term treatment. The authors developed an individualized method of assessing improvement in patients' major areas of impairment over the course of treatment. Using the new approach and two more traditional methods, the authors evaluated the outcome of 37 discharged long-term patients of a private psychiatric hospital who had been rated at admission and discharge on 21 variables related to ego function; affective symptoms; risk of suicide, self-destructiveness, and violence; substance abuse; level of treatment alliance; and, at discharge only, on overall level of improvement. Although the traditional methods failed to show a correlation between length of stay and most of the variables, the individualized approach found that a longer hospital stay was related to greater improvement in areas of most impaired functioning.

Adult↗
PubMed1986

Automated production and analysis of echo contrast agents.

To develop and standardize contrast agents for use in contrast echocardiographic imaging, microbubble size, concentration, decay, and ultrasound backscatter must be known. These parameters were assessed with a scanning laser particle counter, a commercial ultrasound unit, and various sonicated intravenous solutions. The scanning laser particle counter proved to be a fast and effective means of evaluating microbubble size, concentration, and stability. In addition, sonication was found to be a reliable and reproducible technique for preparing standardized echo contrast agent solutions containing uniformly small microbubbles. The bubbles generated ranged in size from 1 to 15 micron in diameter. All solutions had mean bubble diameters less than 6 micron. The half life of solutions ranged from 44 +/- 12 seconds for Hypaque 50%, to 253 +/- 73 seconds for Iopamidol. Addition of the surfactant to dextrose 70% prolonged bubble half life from 58 +/- 12 seconds to 1018 +/- 276 seconds. Phased array two-dimensional echocardiography of sonicated microbubble solutions, and subsequent videodensitometric analysis, revealed that bubble concentration was directly proportional to echo-reflective properties, and that the solutions have significant ultrasound reflective properties in vitro at concentrations of less than 1500 bubbles/ml.

Autoanalysis↗
PubMed1986

Quantitation of echo-contrast effects.

With the recent development of sonicated microbubble echocardiographic contrast agents, it is now reasonable to attempt to quantitate actual tissue perfusion. However, this requires an understanding of the quantitative relationship between microbubble concentrations and the reflected ultrasound signal. This paper describes (1) the basic acoustic properties of sonicated microbubbles, and (2) experimental verification of this relationship, showing that the ultrasound signal actually begins to decrease at a critical concentration that may be predicted based upon bubble size. These microbubbles have acoustic properties that are essentially those of a random collection of Rayleighian scatters. Signal strength is governed primarily by the compressibility of gas, as opposed to fluid. In addition, bubble diameter is an important factor in determining signal strength (sixth power dependence). And, because the bubbles are randomly arranged, the reflected signal is not as great as might be expected, when compared to the signal reflected by a single bubble. A simple in vitro test of the acoustic analysis confirmed the critical limit for bubble concentration, the measurement of which led to a prediction for sonicated microbubble size that is within a factor of two of the published values. This acoustic analysis and confirmation, along with ongoing in vivo experimentation, promises to make possible quantitative regional perfusion measurement employing sonicated contrast agents.

Contrast Media↗