Eliot Corday

Two-Dimensional Contrast Echocardiography. I. In Vitro Development and Quantitative Analysis of Echo Contrast Agents

To facilitate the passage of echo contrast agents through the microcirculation and the echocardiographic study of myocardial perfusion, ultrasonic energy (sonication) was employed to produce contrast agents consisting of relatively uniform, stable and small (less than 10 mu diameter) gaseous microbubbles suspended in liquid solutions. The size and persistence of the microbubbles was verified by light microscopy and an in vitro system were employed for comparative assessment of peak echo amplitude and echo persistence characteristics of various contrast agents. The study indicated that although a variety of hand-agitated and sonicated contrast agents provided satisfactory echo intensities, sonication was clearly superior to the hand-agitation method, because sonication produced smaller, more uniform and more stable microbubbles that may be suitable for myocardial contrast echocardiography. It is concluded that of the contrast agents examined, sonicated solutions of sorbitol (70%) and dextrose (70%) appeared to have particular potential because of the small sizes of the microbubbles (6 +/- 2 and 8 +/- 3 mu, respectively) and their prolonged in vitro persistence. The use of sonication to produce standardized, small and stable microbubbles should facilitate physiologic passage of the contrast agent through the capillary beds and allow two-dimensional imaging of the left heart myocardium during right-sided, aortic root, coronary sinus or intracoronary contrast injections.

Myocardial contrast echocardiography: a reproducible technique of myocardial opacification for identifying regional perfusion deficits.

The effects and reliability of a simple method of contrast two-dimensional echocardiographic delineation of myocardium after intracoronary injections were evaluated in closed-chest dogs. Multiple injections of an agitated saline-Renografin (meglumine diatrizoate) mixture (3:2 ratio, 2-ml bolus) into the left main coronary artery as well as at different sites of the left anterior descending and circumflex coronary arteries were studied in several short-axis and long-axis cross sections of the left ventricle. These contrast injections opacified specific regions of left ventricular myocardium depending on the site of injection. Contrast injection into the left main coronary artery provided a clear, echo-free outline (negative contrast) of underperfused myocardium distal to the coronary occlusion. Reproducibility studies of the extent of involved zones measured in echocardiographic cross sections indicated high intra- and interobserver correlation coefficients (r = 0.97 and 0.97). The effects of the intracoronary injection of contrast material appeared minor and brief. ECG ST-T changes lasted 49.4 ± 36.7 seconds, aortic systolic pressure was reduced by 7.6 ± 4.4% for 18.9 ± 4.8 seconds, and the peak rate of left ventricular pressure rise decreased by 14.3 ± 2.6%, but returned to control levels within 19.4 ± 6.1 seconds. The zone of left ventricular asynergy after coronary occlusions was also delineated by cross-sectional echocardiography and corresponded to the contrast-outlined underperfused zone (negative contrast). This new intracoronary echocardiographic technique has only minor hemodynamic consequences and provides reliable quantitation of underperfused and dysfunctioning zones after experimental coronary occlusions. Further investigation and validation of this method may provide useful characterization of the extent and severity of myocardial ischemia and infarction.

Microbubble dynamics visualized in the intact capillary circulation

The potential for the use of contrast echocardiography to study myocardial perfusion has generated efforts to develop standardized echo contrast agents. The two methods used in this laboratory to generate microbubbles in solutions serving as contrast agents included the widely used hand-agitation method and the newer ultrasonic microcavitation (sonication) method. The latter has been demonstrated to generate smaller and more uniform microbubbles in an in vitro system. The present study was designed to observe, by direct microscopic examination of a cat mesentery preparation, the behavior and fate of the microbubbles in an in vivo system. The in vivo mesentery observations confirm the critical role of microbubble size in its unhindered passage through the capillary vasculature. The smaller and more uniform sonicated microbubbles passed rapidly through the microcirculation along with the red blood cells, whereas the larger microbubbles were observed to coalesce and interrupt the flow of blood and subsequently collapse or shrink.

Quantitation of regional cardiac function by two-dimensional echocardiography. I. Patterns of contraction in the normal left ventricle.

Regional differences in wall motion and wall thickening were quantitated in the normal left ventricle using two-dimensional echocardiography (2-D echo). Using a computer-aided system, the left ventricle was subdivided in a standardized manner into 40 segments of five 2-D echo short-axis cross sections from the mitral valve level to the low left ventricle or apex. Measurements of sectional and segmental cavity areas, muscle areas and endocardial as well as epicardial peritneters, allowed assessment of contractile function using such indexes as endocardial systolic fractional area change (FAC), wall thickening (WTh), and circumferential fiber shortening (shortening). In 50 normal anesthetized, closed-chest dogs (including 10 studies in the conscious state) and in 32 normal humans, left ventricular contractile function increased significantly from base to apex. Thus, in anesthetized dogs, sectional FAC, WTh and shortening increased from left ventricular base to apex as follows: 39.4 ± 5.1% to 61.6 ± 7.2%, 20.5 ± 6.6% to 46.7 11.5% and 22.7 ± 3.4% to 35.4 5.9%, respectively. Similar trends were noted in conscious dogs. In man, sectional FAC, WTh and shortening also increased from the mitral valve to the low left ventricular level: 38.8 3.3% to 60.7 4.5%, 23.9 ± 5.6% to 28.9 ± 7.6% and 21.4 ± 5.0% to 30.6 ± 5.6%, respectively. Detailed segmental analysis in individual cross sections also revealed regional differences in contraction. Generally, contraction was most vigorous in posterior regions of the left ventricle. The septal regions exhibited lowest contraction at the base, but also the greatest increase from base to apex, both in the canine and human. Lateral regions did not show significant changes along the length of the left ventricle. Diastolic wall thickness also varied. We conclude that contraction in the normal left ventricle cannot be assumed to be uniform or symmetrical. These normal regional differences in function should be taken into account when evaluating altered physiologic states and in studying effects of therapeutic interventions.

Torsion of the left ventricle during the ejection phase in the intact dog

Torsion of the left ventricle (LV) is associated with rotation of the apex with respect to the base around the long axis of the LV. A mathematical model of LV mechanics, which relates torsion to transmural distribution of fibre shortening, was evaluated with two-dimensional echocardiography in nine anaesthetised closed-chest dogs. Torsion was calculated as the difference between the angles of rotation (radians) of echo-derived transverse cross-section projections of the LV obtained at the mitral valve and low papillary level, divided by the axial distance between these projections measured in a long-axis cross-section, and multiplied by the outer radius in a mid-papillary transverse projection of the LV. A shortening to torsion ratio (STR) was defined as the ratio of inner wall shortening to torsion occurring during ejection. In a series of 11 measurements, each based on frame-to-frame analysis of 15 cardiac cycles, STR was found to be 2.31 +/- 0.23 rad-1 (mean +/- SD), whereas the mathematical model predicted a STR value of 2.4 rad-1 over a wide range of preload, afterload and contractility levels. We conclude that two-dimensional echocardiography validates the presence of torsion in the normal canine left ventricle, as predicted by the model of left ventricular mechanics.

Two-Dimensional Contrast Echocardiography. II. Transpulmonary Studies

A method using contrast two-dimensional echocardiography for left ventricular chamber and myocardial opacification from a right-sided pulmonary capillary wedge position is described. A total of 152 studies were carried out in nine mongrel dogs. Four different catheters with different catheter tip cross-sectional areas (varying from 0.75 to 2.3 mm2) were used. In addition, catheter position (six different positions in the pulmonary circulation), pressure of injection and type of echo contrast agent (hand-agitated and sonicated) were studied. In all 152 studies, two independent observers agreed that echo contrast was seen in the left ventricular chamber after a pulmonary capillary wedge injection of 8 cc of echo contrast agent followed by a flush injection of 8 cc saline solution. In 71% of the studies, the two independent observers agreed about the degree of opacification on a qualitative scale of 0 to 3+. Time from injection from the catheter tip to the appearance of echo contrast in the left atrium was 6.2 +/- 4.8 seconds for sonicated Renografin-76 and 2.8 +/- 0.6 seconds for sonicated sorbitol 70% (p less than 0.05). Correlation for the disappearance rate of echo contrast as determined for the region in the mid left ventricular chamber and thermodilution cardiac output was fair (r = -0.78; n = 14). In 24 studies, it was not possible to demonstrate the appearance of echo contrast in the myocardium. Peak videointensity of 10 duplicate injections showed a mean percent error of 10.4 +/- 2.1% for sonicated Renografin-76 and 1.4 +/- 0.8% for sonicated sorbitol 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

EFFECT OF THE CARDIAC ARRHYTHMIAS ON THE CORONARY CIRCULATIONS

Excerpt This study will consider the hemodynamic disturbances of the coronary flow which occur during cardiac arrhythmias. It has been shown that fast cardiac arrhythmias can precipitate severe dis...

Myocardial contrast two-dimensional echocardiography: Experimental examination at different coronary flow levels

Regional myocardial echo contrast appearance-disappearance after intracoronary contrast agent injection was examined with computerized two-dimensional contrast echocardiography in eight open chest dogs during successive variation of the coronary blood supply. A new sonication method applied to dextrose 50% produced an echo contrast agent with a microbubble size of 12 +/- 6 mu (mean +/- standard deviation), and 1 cc of this agent was injected into a coronary artery during the echocardiographic study of the left ventricle. Left anterior descending or circumflex coronary artery flow, measured by electromagnetic flowmeter, was successively reduced up to 90% with an extravascular hydraulic occluder, or else increased 40 to 60% through intravenous dipyridamole infusion (7 to 10 micrograms/kg per min). The corresponding myocardial echo time-intensity curves were analyzed for each of 12 segments of a midventricular short-axis cross section. Several potential indexes of myocardial perfusion were derived: peak echo contrast intensity, time from echo contrast appearance to peak intensity, half-life of echo contrast decay phase (T 1/2) and total duration of contrast appearance-disappearance. Except for peak intensity, all of these indexes provided significant (p less than 0.05) differentiation between control coronary flow (66 +/- 17 ml/min) and greater than 50% flow reductions (26 +/- 6 ml/min) or hyperemia (115 +/- 17 ml/min). Half-life values were 5.2 +/- 0.3 seconds for the control state, 9 +/- 2 seconds for the reduced coronary flow and 2 +/- 2 seconds for dipyridamole hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of shock and of vasopressor drugs on the regional circulation of the brain, heart, kidney and liver

W ITH the recent widespread use of vasopressor drugs in the treatment of shock, controversial evidence regarding their efficacy is accumulating. It has been suggested that these agents may have a deleterious effect upon certain organs and may even cause necrosis in the liver and kidney [7,2]. If this is true, the free use of these drugs in shock must be seriously questioned. In order better to understand the rationale of vasopressor therapy, the effect of shock and of vasopressor drugs on blood flow to vital organs was investigated in the experimental animal. Although regional blood flow to these organs has been studied extensively in the past, there is still some disagreement regarding the effect of shock and of vasopressor agents on these organs. This is particularly true of the splanchnic region. In the past, most determinations of blood flow through the liver and kidney have utilized the Fick principle, bromsulphalein excretion being used for the liver [3-S] and clearance usually of paraaminohippuric acid for the kidney [P-71]. These indirect methods of blood flow determination depend upon the functional integrity of the parenchymal cells of the organs studied and are therefore subject to large errors in shock states in which ischemia may severely disturb cellular function [II]. A different technic for these measurements was clearly desirable. The regional flow in shock was therefore reinvestigated, using a flowmeter that allowed continuous flow measurements of many organs at the same time. Using the photoelectric dropmeter, it was possible to measure blood flow directly and continuously in the hepatic artery, portal vein, renal vein, coronary artery and carotid artery. Such direct continuous measurements of blood flow, made in several organs simultaneously, minimized the large error in flow measurement and gave a more complete picture of what happens to blood flow through these organs during all phases of acute shock and vasopressor therapy. Observations were made only during the acute phase of shock. No attempts were made to study the hemodynamics of prolonged, irreversible shock.

Two-dimensional echocardiographic contrast assessment of pacing-induced mitral regurgitation: relation to altered regional left ventricular function

Two-dimensional echocardiography during agitated saline contrast injections into the left ventricle was applied in eight closed chest dogs to examine the degree of mitral valve regurgitation encountered with pacing from two sites: 1) at the right ventricular apex and 2) within the coronary sinus at the base of the left ventricle. Pacing was at a rate of 10 beats/min above the sinus rate, and ranged from 60 to 120 beats/min. Hemodynamic variables were monitored, and data on global and regional left ventricular function were derived from a series of short- and long-axis cross-sectional echographic images. The degree of valvular regurgitation was assessed independently by two observers, and systolic appearance of echo contrast in the left atrium was graded as 0 to +4. Although no mitral regurgitation was noted in sinus rhythm, regurgitation was severe with right ventricular apical pacing (3.2 +/- 0.7, mean +/- standard deviation) and relatively mild (0.9 +/- 0.7) with basal pacing (p less than 0.01 and 0.05, respectively). Relative to sinus rhythm, thermodilution stroke volume was significantly (p less than 0.05) depressed by both apical and basal pacing (from 32.6 +/- 14.6 to 25.0 +/- 7.9 and 26.0 +/- 7.6 cc, respectively), but there was no significant difference between the two pacing sites. Mapping of regional function at six levels of the left ventricle revealed significant heterogeneities, with maximal dysfunction noted in the vicinity of the pacing site. It is concluded that significant differences in mitral regurgitation exist depending on the site of pacing, with apical pacing causing severe regurgitation and abnormal regional contraction near the pacing site.