Suad Ismail

Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection.

BackgroundThe purpose of this study was to determine whether myocardial perfusion can be quantified with myocardial contrast echocardiography using left atrial (LA) injection of contrast. Methods and ResultsBased on a series of in vitro and in vivo experiments, the optimal dose of sonicated albumin microbubbles injected into the LA for establishing a linear relation between video intensity and blood volume in the anterior myocardium was determined. In 10 open-chest dogs, myocardial blood flow (MBF) was augmented by increasing myocardial blood volume (MBV) with an intravenous infusion of phenylephrine HCl. In the presence of this drug, left anterior descending artery stenosis was produced, followed by release of stenosis, to change MBF within the anterior myocardium. MBV was calculated by dividing radiolabeled microsphere-derived MBF by microbubble transit rate. There was close coupling between MBF and MBV in the anterior myocardium during LA injection of contrast (y=1.0x−0.03, SEE=1.07, r=.92, P<.001). An excellent correlation was also noted between background-subtracted peak video intensity and MBV (y=0.24x+0.73, SEE=0.36, r=.88, P<.001). On multivariate analysis, background-subtracted peak video intensity correlated best with MBV. ConclusionsMyocardial perfusion can be quantified from time-intensity curves derived from the anterior myocardium after LA injection of contrast. Background-subtracted peak video intensity in this situation correlates closely with MBV. When MBV and MBF are closely coupled, such as during inotropic stimulation of the heart, background-subtracted peak video intensity also correlates closely with MBF. Since there are similarities in the models of LA and venous injections, these data indicate that it may be feasible to quantify myocardial perfusion with myocardial contrast echocardiography after venous injection of contrast.

Dobutamine echocardiography for determining the extent of myocardial salvage after reperfusion. An experimental evaluation.

BackgroundAlthough dobutamine echocardiography is being increasingly used to determine the presence of viable myocardium in patients who have undergone successful reper-fusion therapy, the physiological basis for such a use has not been clearly defined. Because postischemic myocardium has contractile reserve, we hypothesized that the absolute degree of wall thickening induced by dobutamine during reflow would be directly related to the amount of myocardium that has escaped necrosis. Methods and ResultsThree groups of 12 dogs each were studied at baseline and during 2 to 6 hours of coronary artery occlusion and 15 minutes of reperfusion. In group 1 dogs, which did not receive dobutamine during any of these stages, percent wall thickening at these stages was 32±6%, −2±6%, and 5 ±6%, respectively, and there was no relation between infarct size and percent wall thickening during reflow (r=.20, P=.51). In group 2 dogs, which received 15 μg/kg per minute of dobutamine at all stages, wall thickening at these stages was 40±8%, 0±8%, and 19±10%, respectively, and a good inverse correlation was noted between infarct size and percent wall thickening during reflow (r= −.81, P=.001). In group 3 dogs, in which wall thickening during reflow was measured both before and during infusion of 15 μg/kg per minute of dobutamine, it was 5±8% and 18±14%, respectively, at these stages. Although the correlation between infarct size and percent wall thickening was poor in the absence of dobutamine (r=.36, P=.26), an excellent inverse correlation was noted between the two in the presence of dobutamine (r= −.93, P<.001). A fair inverse correlation was also noted between infarct size and the absolute change in wall thickening induced by dobutamine (r= −.72, P<.01). Maximal wall thickening was noted at a dobutamine dose of 15 μg/kg per minute, and lower doses did not elicit thickening in the presence of larger infarcts despite the presence of viable myocardium. ConclusionsWhen myocardial necrosis coexists with post-ischemic myocardial dysfunction and no residual coronary stenosis, the absolute degree of wall thickening during dobutamine can be used to determine the extent of myocardium that has escaped necrosis. The dose of dobutamine needed to elicit maximal thickening of the postischemic myocardium is related to the amount of myocardial necrosis.

Coronary Reserve Abnormalities in the Infarcted Myocardium Assessment of Myocardial Viability Immediately Versus Late After Reflow by Contrast Echocardiography

BACKGROUND The aim of this study was to determine whether myocardial contrast echocardiography (MCE) during exogenous vasodilation can accurately delineate infarct size, and hence the extent of myocardial viability, both immediately (15 minutes) and late (3 hours) after reperfusion when postreflow coronary hyperema is still present. METHODS AND RESULTS Twenty-one open-chest anesthetized dogs underwent 3 to 6 hours of coronary occlusion followed by reperfusion. MCE was performed 15 minutes after reflow before and during infusion of 0.2 mg.kg-1.min-1 adenosine i.v.. In 12 dogs, infarct size was measured at this time. In the remaining 9 dogs, reperfusion was continued for 3 hours, when MCE was repeated before and after an infusion of 0.56 mg.kg-1.min-1 dipyridamole i.v. and infarct size was measured. In the absence of adenosine, MCE perfusion defect at 15 minutes underestimated infarct sizes at both 15 minutes and 3 hours, whereas in the presence of adenosine, the estimate of infarct size was more accurate. Similarly, in the absence of dipyridamole, although MCE perfusion defect underestimated infarct size (both measured 3 hours after reflow), in the presence of dipyridamole, the estimate of infarct size was more accurate. CONCLUSIONS By unmasking abnormalities in flow reserve within the infarct bed, MCE in conjunction with coronary vasodilators can accurately predict infarct size both 15 minutes and 3 hours after reperfusion. Thus, MCE can be used for assessing the extent of myocardial viability both immediately and late after reperfusion when postreflow coronary hyperemia is still present.

Albumin Microbubble Persistence During Myocardial Contrast Echocardiography Is Associated With Microvascular Endothelial Glycocalyx Damage

BACKGROUND We hypothesized that the persistence of albumin microbubbles within the myocardium during crystalloid cardioplegia (CP) infusion and ischemia-reperfusion (I-R) occurs because of endothelial injury. METHODS AND RESULTS The myocardial transit rate of albumin microbubbles was measured in 18 dogs perfused with different CP solutions and in 12 dogs undergoing I-R. Electron microscopy with cationized ferritin labeling of the glycocalyx was performed in 9 additional dogs after CP perfusion and in 3 additional dogs undergoing I-R. Microbubble transit was markedly prolonged during crystalloid CP perfusion. The addition of whole blood to the CP solution accelerated the transit rate in a dose-dependent fashion (P<0.05), which was greater with venous than with arterial blood (P<0.05). The addition of plasma or red blood cells to CP solutions was less effective in improving transit rate than addition of whole blood (P<0.05). Microbubble transit rate was independent of the temperature, K+ content, pH, PO2, osmolality, viscosity, and flow rate of the perfusate. Similarly, a proportion of microbubbles persisted in the myocardium after I-R, which was related to the duration of ischemia (P<0.01) but not of reflow. Crystalloid CP perfusion and I-R resulted in extensive loss of the endothelial glycocalyx without other ultrastructural changes. This effect was partially reversed in the case of crystalloid CP when it was followed by blood CP. CONCLUSIONS Sonicated albumin microbubbles persist within the myocardium in situations in which the endothelial glycocalyx is damaged. The measurement of the myocardial transit rate of albumin microbubbles may provide an in vivo assessment of endothelial glycocalyx damage.

Relation Between Air-Filled Albumin Microbubble and Red Blood Cell Rheology in the Human Myocardium Influence of Echocardiographic Systems and Chest Wall Attenuation

BACKGROUND We have previously shown that the intravascular rheology of sonicated air-filled albumin microbubbles is similar to that of red blood cells (RBCs) and that their myocardial transit rate is also similar to that of RBCs in the beating canine heart. In the present study, we tested the hypothesis that the myocardial transit rates of these microbubbles reflect those of RBCs in humans at different coronary flow rates. METHODS AND RESULTS RBC and microbubble transit rates were measured in 17 patients undergoing coronary angiography: in 8, measurements were made only at rest, whereas in 9, they were performed both at rest and during a pacing-induced increase in coronary blood flow. A gamma-variate function was used to derive mean RBC and microbubble transit rates from the time-activity and time-intensity plots after the left main injection of RBCs and microbubbles, respectively. There was linear correlation between the myocardial transit rates with both tracers with the slope of the correlation determined by the specific echocardiographic system that was used. Microbubble transit rate consistently overestimated RBC transit rate due to artificial narrowing of the time-intensity curves caused by chest wall attenuation of the echocardiographic signal, which was confirmed through in vitro experiments. CONCLUSIONS There is close correlation between air-filled albumin microbubbles and RBC rheology in the human myocardium. The use of these microbubbles in the cardiac catheterization laboratory could, therefore, provide further insights into myocardial blood flow/myocardial blood volume relations in humans.

Detection of Coronary Stenoses and Quantification of the Degree and Spatial Extent of Blood Flow Mismatch During Coronary Hyperemia With Myocardial Contrast Echocardiography

BACKGROUND We hypothesized that the degree and spatial extent of blood flow mismatch in beds supplied by stenoses that are not flow-limiting at rest can be quantified with myocardial contrast echocardiography (MCE) using left atrial (LA) and right atrial (RA) injections of contrast during pharmacologically induced coronary hyperemia. METHODS AND RESULTS In 12 open-chest dogs, MCE was performed and myocardial blood flow (MBF) was measured by use of radiolabeled microspheres at baseline and during phenylephrine-induced coronary hyperemia. In the presence of this drug, stenoses were placed during different stages on the left anterior descending (LAD) and left circumflex (LCx) coronary arteries, and MCE and MBF assessments were performed. LA injections of 2 mL of 0.5 billion/mL microbubbles (mean diameter, 4.3 microns) were performed at each stage in all 12 dogs, and RA injections of 10 mL of 6 billion/mL microbubbles (mean diameter, 3.7 to 5.3 microns) were administered in 7 dogs. MCE images in which the contrast disparity between the LAD and LCx beds was maximal were digitally subtracted from precontrast images, and mean videointensities in these beds were measured after the dynamic range of gray-scale intensities was increased in the subtracted image and the image was color coded. The region showing hypoperfusion during LAD stenosis was planimetered and expressed as a percentage of the myocardial area in the short-axis slice. There was an excellent correlation between the LAD/LCx bed videointensity ratio and LAD/LCx bed MBF ratio (y = 0.5x + 0.44, r = .91, P < .001) during 57 LA injections. There was also an excellent correlation between the hypoperfused bed size on MCE during LA injection of contrast in the presence of LAD stenosis and the hypoperfused myocardium as determined by radiolabeled microspheres (y = 0.8x + 4.2, r = .90, P < .001, SEE = 2.4, n = 11). The anterior myocardium was opacified in 6 dogs receiving RA injections of contrast, and the hypoperfused area during LAD stenosis correlated closely with that determined by radiolabeled microspheres (y = 0.86x + 3.4, r = .93, P < .01). CONCLUSIONS Coronary stenoses, which are not flow limiting at rest, can be detected and the degree and spatial extent of blood flow mismatch during pharmacologically induced coronary hyperemia can be quantified with MCE using LA and RA injections of contrast. Thus, it is possible that the severity of coronary stenoses and the quantum of myocardium in jeopardy could be quantified in the future with MCE using venous injection of contrast.

Contractile Versus Microvascular Reserve for the Determination of the Extent of Myocardial Salvage After Reperfusion

Background We hypothesized that microvascular reserve is a better indicator of the extent of viable myocardium postinfarction than contractile reserve, especially in the presence of a residual stenosis of the infarct-related artery. Methods and Results Fifteen dogs with various infarct sizes were studied after reperfusion. Contractile reserve, studied by use of dobutamine echocardiography, and microvascular reserve, studied by use of myocardial contrast echocardiography, were measured both before and after creation of a stenosis. In the absence of a stenosis, the relation between infarct size, expressed as percent of risk area, and wall thickening improved with increasing doses of dobutamine (r=.41, .71, and .90 for 5, 10, and 15 μg·kg−1·min−1, respectively; P<.01 for dobutamine 15 μg·kg−1·min−1). In the presence of a stenosis, however, the relation was poor for all doses of dobutamine (r=.22, .57, and .32 for 5, 10, and 15 μg·kg−1·min−1, respectively; P<.01 for 15 μg·kg−1·min−1 dobutamine in the absence ...

Deoxygenated blood minimizes adherence of sonicated albumin microbubbles during cardioplegic arrest and after blood reperfusion: Experimental and clinical observations with myocardial contrast echocardiography

Both administration of cardioplegic solution and blood reperfusion result in endothelial dysfunction. The transit rate of albumin microbubbles during myocardial contrast echocardiography may reflect endothelial injury. Accordingly, we performed myocardial contrast echocardiography in 12 dogs undergoing cardiopulmonary bypass and measured the myocardial transit rate of microbubbles injected into the aortic root during delivery of cardioplegic solutions containing arterial and venous blood and delivery of pure crystalloid cardioplegic solution. The myocardial transit rate of 99mTc-labeled red blood cells was measured and perfusates were sampled for biochemical analysis at each stage. The microbubble transit rate was markedly prolonged during delivery of crystalloid cardioplegic solution and improved significantly during infusion of blood cardioplegic solution (p < 0.001); venous compared with arterial blood in the solution resulted in a greater rate (p < 0.001). The microbubble transit rate did not correlate with pH, oxygen tension or carbon dioxide tension values, or K+ concentration. The red blood cell transit rate remained constant regardless of the cardioplegic perfusate infused. Myocardial contrast echocardiography was also performed in 12 patients undergoing coronary artery bypass who underwent sequential arterial and venous reperfusion after cardioplegic arrest. The microbubble transit rate was faster with venous than arterial blood reperfusion (p = 0.01), although this gain was diminished when arterial blood reperfusion preceded venous blood reperfusion (p = 0.05). Our results indicate that endothelial dysfunction after cardioplegic arrest may be ameliorated by reperfusion with venous rather than arterial blood.

Transpulmonary Transit of Microbubbles During Contrast Echocardiography: Implications for Estimating Cardiac Output and Pulmonary Blood Volume

We postulated that the pulmonary transit rate of sonicated albumin microbubbles, which have an intravascular rheology similar to that of red blood cells, would be directly proportional to cardiac output (CO) and inversely proportional to pulmonary blood volume (PBV). Accordingly, 4 ml of Albunex ultrasound contrast agent (0.5 billion/ml of 4.3 mu bubbles) was injected into the right atrium of six dogs (Group I) during simultaneously performed two-dimensional echocardiography, and the time between the initial appearance of the bubbles in the right and left ventricle, respectively, was measured. CO was either increased (by intravenous infusion of 15 micrograms/kg/min of dobutamine) or decreased (by producing left ventricular ischemia or by administering 2 mg of intravenous propranolol) in a random order and microbubbles were injected again. At each stage, thermodilution CO was measured. There was a close linear relation between CO and pulmonary transit rate of Albunex in each dog with the correlation coefficient ranging from 0.79 to 0.99, with a mean of 0.92. Pulmonary blood volume was derived in each dog from the reciprocal of the slope of the regression between CO and pulmonary transit rate and varied from 106 to 261 ml in the six dogs with a mean value of 178 +/- 64 ml. There was excellent interobserver and intraobserver correlation (r = 0.99 each) for determining the pulmonary transit rate of Albunex. The reproducibility of pulmonary transit rate estimation from repeated contrast injections at the same hemodynamic state in another group of six dogs (Group II) was also good (r = 0.99). It is concluded that the pulmonary transit rate of Albunex ultrasound contrast agent can be used to assess directional changes in CO and to measure pulmonary blood volume. This method may have clinical applications.

Integrated backscatter and digital acquisition during myocardial contrast echocardiography: Is there an advantage over conventional echocardiography for intracoronary injections?

This study was designed to answer the question of whether, despite their theoretic superiority, integrated backscatter imaging (IBS) and digital data acquisition (DA) offer any advantage over conventional echocardiography (CE) during quantitative myocardial contrast echocardiography. In vitro experiments were performed (1) to determine the microbubble concentration versus videointensity relationships for CE and IBS and (2) to define the relationship between flow through and microbubble transit rates for CE and IBS. These data were stored on videotape. In vivo experiments were performed whereby microbubbles were injected into the left anterior descending artery at different flow rates in 14 dogs and IBS and CE data were stored both in digital format and on videotape. Although the level of compression did not affect the microbubble concentration versus videointensity plots during IBS compared with CE, in practical terms the mean transit rate, peak intensity, and area under the curve were not affected by the level of compression for both forms of imaging as long as the postprocessing used for CE imaging was linear and the microbubble dose was small. In addition, although DA resulted in higher peak intensity and area under the curve compared with storage on videotape because of its broader dynamic range, the correlation between these measurements was excellent with both forms of image storage. We conclude that, although differences exist between CE and IBS and between Da and analog acquisition, these differences do not significantly affect the derivation of parameters from time-intensity plots during myocardial contrast echocardiography when contrast material is injected into a coronary artery.