Delivery of bevacizumab to atheromatous porcine carotid tissue using echogenic liposomes.

Ultrasound is both a valuable diagnostic tool and a promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. Vascular effects can be mediated by mechanical oscillations of circulating microbubbles that may also encapsulate and shield therapeutic agents in the bloodstream. Here, the effect of color-Doppler ultrasound exposure on bevacizumab-loaded liposome delivery into the vascular bed was assessed in atheromatous porcine carotids. Bevacizumab, an anti-angiogenic antibody to vascular endothelial growth factor (VEGF-A), was loaded into echogenic liposomes (BEV-ELIP) and confirmed to be immunoreactive. BEV-ELIP flowing within the lumen were exposed to color-Doppler ultrasound at three acoustic pressures for 3.5 min during treatment at physiologic temperature and fluid pressure. To confirm the presence of bubble activity, cavitation was detected within the lumen by a single-element passive cavitation detector. After treatment, the artery was fixed at physiologic pressure and subjected to immunohistochemical analysis to assess the penetration of bevacizumab within the carotid wall. The results suggest that other factors may more strongly influence the deposition of bevacizumab into carotid tissue than color-Doppler ultrasound and cavitation. In both sets of arteries, preferential accumulation of bevacizumab occurred in locations associated with atheroma progression and neointimal thickening: fibrous tissue, necrotic plaque and areas near macrophage infiltration. The delivery of bevacizumab to carotid vascular tissue correlated with the properties of the tissue bed, such as permeability, or affinity for growth-factor binding. Future investigations using this novel therapeutic strategy may focus on characterizing the spatial extent of delivery and bevacizumab colocalization with biochemical markers of atheroma.

Asymptomatic aneurysm of the interatrial septum.

A case of interatrial septal aneurysm discovered by two-dimensional echocardiography and confirmed by ultrasound contrast technique is described. Previous reports are reviewed, emphasizing the differential diagnosis, prognosis and recommendations for follow-up.

Ultrasound study of acoustic properties of the normal canine heart: comparison of backscatter from all chambers.

Much effort has recently been directed toward ultrasound characterization of normal and abnormal left ventricular myocardium. The purpose of this study was to evaluate the normal acoustic properties of all four cardiac chambers as a first step toward tissue characterization of the atria and ventricles. The hypothesis was that integrated ultrasound backscatter would follow the pattern of collagen concentration in the cardiac chambers, being higher in the right side of the heart than in the left and in the atria compared with the ventricles. Seven normal canine hearts, perfusion-fixed in 10% formalin, were examined. Sections of the free walls of right and left ventricles and atria were studied in vitro with a 5 MHz transducer positioned at the focal distance from the epicardium. The radio frequency ultrasound signal energy from each specimen was derived, corrected for sample thickness and expressed as integrated backscatter, in decibel units less than the reflected energy from a stainless steel block. The backscatter was higher from the right ventricle than from the left ventricle (-64.5 +/- 1.25 [mean +/- SEM] [n = 7] versus -73.6 +/- 1.32; p less than 0.05), higher from the right atrium than from the right ventricle (-58.5 +/- 0.83 versus -64.5 +/- 1.25; p less than 0.05) and higher from the left atrium than from the left ventricle (-62.8 +/- 1.14 versus -73.6 +/- 1.32; p less than 0.05). These data show that backscatter is higher in the right ventricle than in the left ventricle and in the atria compared with the ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary arterial remodeling studied by high-frequency epicardial echocardiography: an early compensatory mechanism in patients with obstructive coronary atherosclerosis.

Coronary arterial remodeling is a compensatory mechanism that may limit the adverse effects of coronary obstructive lesions by expansion of the entire vascular segment. To determine if this compensatory anatomic change occurs in patients, high-frequency epicardial echocardiography using a 12 MHz transducer was performed during open heart surgery in 33 patients (10 with normal coronary arteries undergoing valvular surgery and 23 with coronary atherosclerosis). From stop-frame videotape high-frequency epicardial echocardiographic images, cross-sectional measurements of luminal area and total arterial area (lumen, intima, media and dense adventitia) were made in the patients with atherosclerosis at the site of arterial lesions and from the most proximal portion of the same artery. Remodeling was defined as enlargement of the total arterial area. In normal arteries measurements were made from proximal and midarterial locations. In the patients with normal coronary arteries, total arterial area, as determined by high-frequency echocardiography, decreased from the proximal site to the midportion of the artery (from 10.4 +/- 0.9 to 8.4 +/- 1.0 mm2, p less than 0.05); luminal area also decreased (from 6.0 +/- 0.6 to 4.5 +/- 0.7 mm2, p less than 0.05). In patients with coronary arterial lesions, luminal area also decreased from the proximal site to the arterial lesion site (from 5.3 +/- 0.6 to 2.3 +/- 0.3 mm2, p less than 0.05), but total arterial area increased (from 11.6 +/- 1.0 to 13.0 +/- 1.0 mm2, p less than 0.05). Of the 25 coronary arteries evaluated, only 4 had angiographic evidence of coronary collateral formation. These data indicate that coronary arterial remodeling is an important compensatory mechanism in obstructive coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic and ventriculographic recovery patterns in Q wave myocardial infarction.

To further define the capacity for recovery after acute phase electrical and mechanical injury in patients with Q wave myocardial infarction who were treated with standard measures, 120 lead body surface potential maps and radionuclide angiograms were recorded at day 5 before discharge and month 6 after infarction in 23 patients with a first infarction (12 anterior and 11 inferior by standard 12 lead electrocardiographic criteria). In addition to assessment of spatial changes in electrocardiographic and wall motion patterns, five quantitative variables were evaluated: minimal Q zone integral, sigma Q wave integral, maximal ST integral, left ventricular ejection fraction and left ventricular wall motion abnormality score. From day 5 to month 6 after infarction, the only change in the inferior infarction group was a gain in sigma Q wave (-91 +/- 40 mu V X s X 10(2) to -68 +/- 24 mu V X s X 10(2); p less than 0.05). In contrast, all variables improved over the same time period in the anterior infarction group: Q zone minimum, -34 +/- 20 to -24 +/- 13 mu V X s (p less than 0.05); sigma Q wave, -160 +/- 122 X 10(2) to -120 +/- 90 mu V X s X 10(2) (p less than 0.05); ST maximum, 44 +/- 19 to 18 +/- 9 mu V X s (p less than 0.01); ejection fraction, 54 +/- 7 to 63 +/- 17% (p less than 0.05); and wall motion score, 6 +/- 3 to 3 +/- 3 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

High frequency epicardial echocardiography for coronary artery evaluation: in vitro and in vivo validation of arterial lumen and wall thickness measurements.

The purpose of this study was to determine the accuracy of a new high frequency echocardiographic technique for the quantitative assessment of coronary artery luminal and wall dimensions. In 32 open chest animals, high frequency echocardiographic measurements (echo) of luminal diameter correlated well with in vitro histologic measurements (Histo) (r = 0.86; high frequency echo = 0.89 Histo + 0.79) (range 1.7 to 5.8 mm). Similar results were found in the evaluation of five human autopsy hearts studied in vitro. Coronary artery wall thickness measurements in human autopsy hearts showed a good correlation with high frequency echocardiographic measurements (r = 0.86; high frequency echo = 0.65 Histo + 0.24) (range 0.3 to 0.8 mm). In eight open chest calves, high frequency echocardiographic measurements of total vessel diameter correlated well with sonomicrometer measurements (Sono) (r = 0.94; high frequency echo = 1.03 Sono + 0.4) (range 2.1 to 5.3 mm). Inter- and intraobserver variability measurements of high frequency echocardiographic measurements demonstrated excellent reproducibility (r = 0.95, interobserver variability for wall thickness; r = 0.97, interobserver variability for luminal diameter; n = 10 postmortem human coronary arteries). In conclusion, high frequency echocardiography is an accurate and reproducible method of measuring coronary luminal and wall geometry and may be a potentially useful tool for in vivo coronary artery evaluation in patients.

In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement.

OBJECTIVES: The purpose of this study was to target acoustically reflective liposomes to atherosclerotic plaques in vivo for ultrasound image enhancement. BACKGROUND: We have previously demonstrated the development of acoustically reflective liposomes that can be conjugated for site-specific acoustic enhancement. This study evaluates the ability of liposomes coupled to antibodies specific for different components of atherosclerotic plaques and thrombi to target and enhance ultrasonic images in vivo. METHODS: Liposomes were prepared with phospholipids and cholesterol using a dehydration/ rehydration method. Antibodies were thiolated for liposome conjugation with N-succinimidyl 3-(2-pyridyldithio) propionate resulting in a thioether linkage between the protein and the phospholipid. Liposomes were conjugated to antifibrinogen or anti-intercellular adhesion molecule-1 (anti-ICAM-1). In a Yucatan miniswine model, atherosclerosis was developed by crush injury of one carotid and one femoral artery and ingestion of a hypercholesterolemic diet. After full plaque development the arteries were imaged (20-MHz intravascular ultrasound catheter and 7.5-MHz transvascular linear probe) after injection of saline, unconjugated liposomes and antibody conjugated liposomes. RESULTS: Conjugated liposomes retained their acoustically reflective properties and provided ultrasonic image enhancement of their targeted structures. Liposomes conjugated to antifibrinogen attached to thrombi and fibrous portions of the atheroma, whereas liposomes conjugated to anti-ICAM-1 attached to early atheroma. CONCLUSIONS: Our data demonstrate that this novel acoustic agent can provide varying targeting with different antibodies with retention of intravascular and transvascular acoustic properties.

Variable morphology of coronary atherosclerosis: characterization of atherosclerotic plaque and residual arterial lumen size and shape by epicardial echocardiography.

The purpose of this study was to evaluate the in vivo characteristics of coronary atherosclerosis by using high frequency epicardial echocardiography. High frequency epicardial echocardiography was used to evaluate residual lumen and wall morphology at the sites of maximal coronary atherosclerosis in 26 patients undergoing coronary artery bypass grafting. The maximal/minimal wall thickness ratio was 3.1 +/- 0.2 (mean +/- SEM) with a large range (1.3 to 7.5). Portions of the wall were normal in 16 of 31 lesions; the percent normal circumference ranged from 9% to 85%. Maximal/minimal lumen diameter ratio was 1.5 +/- 0.1 (range 1.1 to 2.9). The shape of the residual coronary lumen was noncircular in 16 lesions: oval in 13 and complex in 3. The residual coronary lumen was eccentrically placed within six arteries. These data emphasize the variability of residual lumen and wall geometry in atherosclerosis.

Validation by high-frequency epicardial echocardiography of a new method of analyzing coronary angiography quantitatively in coronary artery disease.

In coronary atherosclerosis, the arterial lumen size and shape can be markedly irregular, eccentric and variable. Traditional angiographic interpretation, emphasizing percent diameter stenosis, has been criticized as an inadequate descriptor of such diseased arteries. Computerized quantitative angiographic technologies, yielding a true lumen area measurement, may be superior. High-frequency epicardial echocardiography (HFEE) is a technique that allows on-line evaluation of coronary arterial wall and lumen at the time of cardiac surgery. It has been extensively validated and yields accurate measurements of normal and diseased coronary lumen areas. This study compares quantitative coronary angiography (QCA) estimates of lumen area to those obtained by HFEE to determine if the computerized angiographic method more accurately predicts residual luminal area than traditional angiographic percent diameter stenosis measurements. Although actual luminal morphology was quite variable, there was a good correlation between lumen areas determined by HFEE versus QCA: r = 0.85, n = 67, HFEE = 0.8 QCA - 0.1 (HFEE 4.0 +/- 0.30 mm2, mean +/- SEM range 0.3 to 14.0; QCA 5.1 +/- 0.40 mm2, range 0.7 to 11.8). Percent diameter stenosis determined from the angiograms did not correlate well with HFEE or QCA measurements of residual luminal area. Separation of "normal" arterial segments (defined as < 25% diameter stenosis) from "abnormal" segments (> 50% diameter stenosis) by angiography did not agree with lumen areas as defined by either HFEE or QCA. Better separation occurred when QCA-determined luminal areas were used to separate normal from abnormal arterial segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequent ventricular ectopic activity without underlying cardiac disease: analysis of 45 subjects.

Forty-five subjects, aged 2 weeks to 62 years, who presented with frequent (greater than 100/day) ventricular ectopic beats (VEBs) and without evidence of underlying cardiac disease were studied. The spectrum of ventricular dysrhythmia was assessed by 24-hour ambulatory electrocardiography and exercise tolerance test. Sinus rhythm was the prevailing rhythm in all subjects. VEB frequency averaged 444 +/- 454 per hour (range 0 to 1,863) over the 24-hour monitoring period and was not significantly different during waking or sleeping periods. There was no simple correlation of VEB frequency with prevailing sinus rate (r = -0.0006; p = not significant [NS]). The prevalence of complex VEBs (multiform, R-on-T and repetitive) was relatively high (18 of 45 patients), and was equally distributed about the median VEB frequency of 314 VEBs/hour (7 of 18 versus 11 of 18; NS). Of the 43 subjects who had exercise tests, 37 had VEBs during the preexercise rest phase, compared with only 11 at peak exercise (p less than 0.0001). To assess the short-term natural history of the VEBs, 27 subjects had repeat clinical examinations and 24-hour electrocardiograms at a mean interval of 8 months. All remained well. Although there was considerable individual temporal variability of VEB frequency in this subgroup, there was no significant change in group mean values (415 +/- 409 VEBs/hour initially versus 401 +/- 383 VEBs/hour at follow-up study; NS). The relative temporal constancy of VEB frequency in the group as a whole was also reflected in a high linear correlation of VEB frequency at initial and follow-up studies (r = 0.816; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Can atherosclerotic coronary arteries vasodilate? An intraoperative high-frequency epicardial echocardiographic study.

Our purpose was to evaluate the vasodilating responses of atherosclerotic coronary arteries using intraoperative high-frequency (12 MHz) epicardial echocardiography. We obtained continuous high-frequency epicardial echocardiographic recordings during surgery, and determined cross-sectional lumen area from 17 coronary arterial segments (12 patients). Nitroglycerin (100 to 400 micrograms/min) was administered intravenously to reduce mean (+/- SEM) arterial pressure 14 +/- 1.8 mm Hg. The cross-sectional arterial images were classified using 3 different parameters: arterial lumen area, percentage of the arterial wall circumference that was atherosclerotic (wall thickness > 0.7 mm), and presence of an eccentrically shaped arterial lumen (maximal/minimal luminal diameter > 1.5). Nine arterial segments had small (< 5.0 mm2) arterial lumens (1.7 +/- 0.40 mm2 [+/- SEM; range 0.6 to 3.9]). With nitroglycerin, the luminal area increased 0.8 +/- 0.28 mm2 (range 0 to 2.5), and 39 +/- 12.1% (range 0 to 117). The remaining 8 segments had larger (> 5.0 mm2) lumens (8.7 +/- 0.91 mm2 [range 5.0 to 11.9]). With nitroglycerin the luminal area increased 4.3 +/- 1.11 mm2 (range 1.4 to 11.4), and 51 +/- 10.2% (range 16 to 96). Seven arterial segments had eccentric lumens; mean maximal/minimal ratio was 1.8 +/- 0.08 (range 1.6 to 2.0). The area increased 39 +/- 7.3% (range 16 to 71) with nitroglycerin. In the 10 concentrically shaped lumens (maximal/minimal lumen diameters 1.3 +/- 0.04 [range 1.1 to 1.5]), nitroglycerin increased luminal area by 48 +/- 12.6% (range 0 to 117) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of caffeine on cardiac rate, rhythm, and ventricular repolarization. Analysis of 18 normal subjects and 18 patients with primary ventricular dysrhythmia.

To determine clinical electrophysiologic effects of a moderate dose of caffeine, we compared prevailing cardiac rhythm and rate, the prevalence and frequency of ventricular dysrhythmia, and Q-T intervals in two populations over an initial 24-hour caffeine-free period and a subsequent 24-hour period in which caffeine was ingested in a dosage of 1 mg/kg of body weight at intervals of one half-life during waking hours. Group 1 was composed of 18 clinically normal subjects; group 2 was 18 subjects with frequent ventricular ectopic beats (VEBs) and no (n = 16) or minor (n = 2) cardiac disease. Sinus rhythm was the prevailing rhythm in all subjects at all times. For group 1, the mean sinus rate during the caffeine-free period was 77 +/- 10 beats per minute, compared to 73 +/- 9 beats per minute during the period of caffeine ingestion (not significant). Similarly, for group 2, the average sinus rate during the caffeine-free period was 76 +/- 11 beats per minute, not significantly different from the average sinus rate during the test period, 76 +/- 10 beats per minute. During abstention from caffeine, four of 18 subjects in group 1 had infrequent (less than 1/hr) VEBs, compared to nine of 18 during caffeine ingestion (not significant). In group 2, some 16 of the 18 subjects had VEBs during the caffeine-free period, with the frequencies varying from less than one VEB per hour to 1,449 VEBs per hour. During the test period, 14 of the 18 subjects in group 2 increased their VEB frequency, and the group's mean frequency rose from 207 +/- 350 VEBs per hour (control period) to 307 +/- 414 VEBs per hour (test period) (p less than 0.01). The Q-T interval in group 1, measured as the corrected Q-T interval (Q-Tc), averaged 0.430 +/- 0.027 during the caffeine-free period, not significantly different from the test period (0.425 +/- 0.019). The comparable Q-Tc values for group 2 were 0.424 +/- 0.018 during the caffeine-free period and 0.433 +/- 0.025 for the period of caffeine ingestion (not significant).(ABSTRACT TRUNCATED AT 400 WORDS)

Indirect measurement of infarct size. Correlative variability of enzyme, radionuclear angiographic, and body-surface-map variables in 34 patients during the acute phase of first myocardial infarction.

To gain a correlative perspective of indirect indications of the size of a myocardial infarct, we measured several body-surface electrocardiographic variables and several enzyme and radionuclear angiographic indicators of an infarct's size in 34 patients during the acute phase of first infarction. We found that bivariate correlations ranged widely, from an r value of 0.05 to an r value of 0.92, but were significantly (p less than 0.001) higher when variables from the same technique were correlated (mean r, 0.60 +/- 0.27), as opposed to correlations of variables from different techniques (mean r, 0.27 +/- 0.18). Trivariate comparisons among techniques produced significantly (p less than 0.001) higher r values, but the highest, an r value of 0.76 (total wall motion abnormality score; peak lactic dehydrogenase level; ST-segment integral maximum), indicated that even in this best case, only about 60 percent of the variation of one variable was dependent on or due to the two other variables. These data demonstrate that multiple indirect quantitative indicators of myocardial injury can vary widely in their correlations within the same population of infarcts, and much remains unknown in their relationships during the acute phase. Caution should be exercised, therefore, in their clinical application to predict an infarct's size in individual patients with acute myocardial infarction.

A method for automatic edge detection and volume computation of the left ventricle from ultrafast computed tomographic images.

RATIONALE AND OBJECTIVES: Detection of endocardial and epicardial borders of the left ventricle (LV) using various imaging modalities is time-consuming and prone to interpretive error. An automatic border detection algorithm is presented that is used with ultrafast computed tomographic images of the heart to compute cavity volumes. METHODS: The basal-level slice is identified, and the algorithm automatically detects the endocardial and epicardial borders of images from the basal to the apical levels. From these, the ventricular areas and chamber volumes are computed. The algorithm uses the Fuzzy Hough Transform, region-growing schemes, and optimal border-detection techniques. The cross-sectional areas and the chamber volumes computed with this technique were compared with those from manually traced images using canine hearts in vitro (n = 8) and studies in clinical patients (n = 27). RESULTS: Though the correlation was good (r = .88), the algorithm overestimated the LV epicardial area by 4.8 +/- 6.4 cm2, though this error was not statistically different from zero (P > .05). There was no difference in endocardial areas (r = .95, P > .05). The algorithm tended to underestimate the end-diastolic volume (r = .94) and the end-systolic volume (r = .94), although these errors were not statistically different from zero (P > .05). The algorithm tended to underestimate the ejection fraction (r = .80), although this error was not statistically different from zero (P > .05). CONCLUSIONS: Automatic detection of myocardial borders provides the clinician with a useful tool for calculating chamber volumes and ejection fractions. The algorithm, with the corrections suggested, provides an accurate estimation of areas and volumes. This algorithm may be useful for contour border identification with ultrasound, positron-emission tomography, magnetic resonance imaging, and other imaging modalities in the heart, as well as other structures.

Development of echogenic, plasmid-incorporated, tissue-targeted cationic liposomes that can be used for directed gene delivery.

RATIONALE AND OBJECTIVES: Echogenic antibody-conjugated anionic liposomes have been developed that allow directed tissue targeting and acoustic enhancement. These are not efficient for gene delivery. A cationic formulation that allows directed gene delivery while retaining acoustic properties may provide more efficient transfection. METHODS: Cationic liposomes were prepared and acoustic reflectivity was determined. Anti-fibrinogen-conjugated liposomes were laid on fibrin-coated slides and adherence was quantified using fluorescence techniques. Liposomes were combined with a reporter gene and plated on cell cultures. Human umbilical vein endothelial cells were stimulated to upregulate intercellular adhesion molecule-1 (ICAM-1) and were treated with anti-ICAM-1-conjugated liposomes, and gene expression was quantified. RESULTS: Cationic liposomes retained their acoustic reflectivity and demonstrated specific adherence to fibrin under flow conditions. Significant transfection of human umbilical vein endothelial cells was demonstrated, with higher gene expression seen with specific antibody-conjugated liposomes. CONCLUSIONS: Novel acoustic cationic liposomes have been developed that can be antibody conjugated for site-specific adherence and directed cell modification. This presents exciting potential for a vector that allows tissue enhancement and targeted gene delivery.

Myocardial acoustics in pediatric allograft rejection.

BACKGROUND: Ultrasonographic tissue characterization is the assessment of physical properties of biologic tissue on the basis of quantitative analysis of its acoustic characteristics. Abnormalities in microscopic structure that occur with cardiac allograft rejection may result in characteristic alterations in myocardial acoustics. Ultrasonographic tissue characterization may allow noninvasive detection of rejection. METHODS: Findings in 22 pediatric heart transplant patients undergoing routine surveillance for rejection by endomyocardial biopsy were prospectively evaluated. Off-line ultrasonographic tissue characterization analysis was done on transthoracic echocardiograms obtained at each biopsy. Within patients, tissue characterization texture measures derived from the ultrasonographic image data were compared with histologic findings. Univariate multiple regression analysis was used to identify texture measures associated with acute allograft rejection in a subgroup (n = 8) with at least one biopsy-proven episode of moderate rejection. RESULTS: Measures of homogeneity (co-occurrence matrix correlation and heterogeneity (run-length nonuniformity) decreased with moderate rejection (p < 0.03). Homogeneity measures decreased if the patient had a previous episode of rejection. Several measures of heterogeneity (gray level difference and run-length statistics) were affected by the presence of edema. Run-length nonuniformity was the only measure that differentiated moderate rejection from edema. Discriminant analysis on all 22 patients correctly identified 96% of first rejection episodes (sensitivity 80%, specificity 64%), 93% of moderate and severe rejection episodes (sensitivity 71%; specificity 62%), and 69% of all rejection episodes (sensitivity 51%, specificity 91%). CONCLUSIONS: Histologic changes associated with moderate and severe pediatric allograft rejection as reflected by characteristic alterations in myocardial acoustics can be assessed with ultrasonographic tissue characterization. Histologic changes associated with transplantation itself (resolution of rejection and edema) also affect myocardial acoustics and must be taken into account in rejection surveillance.

Structural evaluation of porcine heart valve prostheses with radiofrequency ultrasound.

BACKGROUND: Bioprosthetic heart valve use is limited by progressive degeneration. Early degenerative changes are often occult, making assessment of tissue integrity difficult. Ultrasound tissue characterization may detect alterations in tissue structure and allow early detection of leaflet degeneration. METHODS: Using a modified echocardiographic unit (Acuson), radiofrequency (RF) integrated backscatter amplitude (IBA) (integral/RF/dt) was measured in 38 leaflets from nine explanted and six control porcine valves. Regions of interest in each leaflet were studied using four ultrasound frequencies. Radiographic gray scale mean and leaflet thickness were measured at each region of interest. Percent collagen and mineral were calculated for each region of interest using color-image processing of histologic sections and compared to IBA. RESULTS: IBA values for control vs. explanted leaflets were (mean value+/-standard deviation): 8.2+/-4.69 dB vs. -4.7+/-4.64 dB at 7.0 MHz; -5.8+/-4.34 dB vs. -3.1+/-5.34 dB at 5.0 MHz; -3.8+/-3.38 dB vs. -2.1+/-3.18 dB at 3.5 MHz; and -9.0+/-4.58 dB vs. -7.1+/-4.25 dB at 2.5 MHz. Collagen content was 27.7+/-8.50% vs. 33.2+/-10.90%, mineral content was 0.1+/-0.10% vs. 2.1+/-4.30%, and radiographic gray scale mean was 150.6+/-1.96 vs. 145.3+/-5.14 for control vs. explanted leaflets, respectively. For control and explanted leaflets IBA, collagen content, mineral content, and radiographic gray scale mean were different (control vs. explanted P<0.05). Leaflet thickness was also noted to be different between the two groups. IBA was different among explanted leaflets with low, medium, and high mineral content. CONCLUSION: IBA was found to be a useful technique to differentiate normal from explanted porcine prosthetic valves in vitro. This method may be useful in the serial assessment of bioprosthetic leaflet degenerative properties in vivo.

Left ventricular functional improvement after transmyocardial laser revascularization.

BACKGROUND: Transmyocardial laser revascularization has been used to treat patients with end-stage coronary artery disease that is not amenable to standard revascularization. Although there is evidence of angina relief and quality of life enhancement, there is little information concerning improvement in myocardial contractility. The purpose of this study was to determine whether transmyocardial laser revascularization improves myocardial function in chronically ischemic myocardium. METHODS: In a model of chronic ischemia by Ameroid occlusion of the circumflex artery, domestic pigs (n = 8) were treated with transmyocardial laser revascularization. Before laser treatment, segmental contraction was assessed at rest and with dobutamine stress echocardiography. Myocardium subtended by the occlusion was compared with that remote from the occlusion. Six weeks after transmyocardial laser revascularization, the animals were restudied at rest and with stress, and then sacrificed. Sham-treated control animals (n = 4) underwent the same procedures but were not treated with transmyocardial laser revascularization. Control animals did not demonstrate significant recovery of function. RESULTS: Transmyocardial laser revascularization improved resting function in chronically ischemic myocardium by 100%. CONCLUSIONS: Transmyocardial laser revascularization significantly improves the function of chronically ischemic myocardium. These data may help explain the mechanisms by which transmyocardial laser revascularization is clinically effective.

Intraoperative high-frequency epicardial echocardiography in coronary revascularization: locating deeply embedded coronary arteries.

During coronary revascularization, the precise location of major coronary arteries may be obscured by overlying fat, myocardial bridging, or epicardial scarring. High-frequency epicardial echocardiography can be used intraoperatively to quickly image and locate such arteries and eliminate the need for time-consuming epicardial exploration or potentially deleterious retrograde probing of distal coronary artery branches. This technique can be applied using commercially available equipment and the aid of a skilled technician.

Functional comparison of transmyocardial revascularization by mechanical and laser means.

BACKGROUND: As a result of the clinical benefit observed in angina patients treated by transmyocardial revascularization (TMR) with a laser, interest in mechanical TMR has been renewed. Although the injury induced by mechanical TMR is similar to laser TMR, the resultant impact on myocardial contractility is unknown. The purpose of this study was to determine whether mechanical TMR improves ventricular function as compared with laser TMR in chronically ischemic myocardium. METHODS: After establishing an area of chronic myocardial ischemia, 25 domestic pigs were randomized to treatment by: excimer laser (group I), a hot needle (50 degrees C) (group II), a normothermic needle (group III), an ultrasonic needle (40 KHz) (group IV), or no treatment (group V). All devices create a transmural channel of the same diameter; 22 +/- 1 transmural channels were created in each animal. Regional myocardial contractility was assessed by measuring ventricular wall thickening at rest and with dobutamine stress echocardiography. Six weeks after revascularization, the animals were restudied at rest and with stress. Postsacrifice and histologic analysis of angiogenesis and TMR effects was then assessed. RESULTS: Laser TMR provided significant recovery of ischemic myocardial function. This improvement in contractility after laser TMR was a 75% increase over the baseline function of the ischemic zone (p < 0.01). Mechanical TMR provided no significant improvement in function posttreatment. In fact, TMR achieved with an ultrasonic needle demonstrated a 40% worsening of the contractility versus the pretreatment baseline (p < 0.05). Histologic analysis demonstrated a significant increase in new blood vessels in the ischemic zone after laser TMR, which was not demonstrated for any of the other groups (p < 0.05). Additionally, evaluation of the mechanical TMR channels demonstrated significant scarring, which correlated with the functional results. CONCLUSIONS: Using devices to create an injury analogous to the laser, mechanical TMR failed to improve the function of chronically ischemic myocardium. Only laser TMR significantly improved myocardial function.