Use of echocardiography to assess function of hDAF-transgenic pig cardiac xenografts.

The current standard of hand palpation may not be a sensitive method to detect rejection in heterotopic heart xenotransplants (HHTx). We sought to assess the use of echocardiography to detect rejection of pig heart xenografts. Four cynomolgus monkeys received HHTx from hDAF-transgenic pigs. Immunosuppression was cyclophosphamide induction, cyclosporine, steroids, sodium mycophenolate, alphaGal trisaccharide polymer, +/-soluble complement receptor type 1. Echocardiography was performed immediately after HHTx and three times a week postoperatively. Contractility on echo was scored as 1(none), 2(severely impaired), 3(moderate to severely impaired), 4(moderately impaired), 5(mild to moderately impaired), 6(mildly impaired), or 7(normal). Left ventricle wall thickness (LVWT) was measured in the anterior, inferior, posterior, lateral, and septal walls, the average was calculated. Impaired contractility or increase in LVWT were considered rejection and treated with steroids (solumedrol 15 mg/kg IV for 3-5 days). Palpation score (4-strong to 1-none) was recorded daily. Myocardial biopsies were obtained infrequently. At the time of first rejection, all four monkeys had an increase in LVWT and a decrease in contractility on echocardiography. Steroid treatment enhanced contractility in four monkeys and decreased LVWT in three monkeys. Palpation score remained at four of four during initial rejection episodes. Decrease in contractility and increase in LVWT on echocardiography appear to signify graft injury because steroid treatment results in improvement. Compared to palpation, echocardiography is more sensitive for assessing function of heterotopic pig heart xenografts. Echocardiography has, therefore, the potential to detect and treat early rejection episodes of heterotopic heart xenografts in nonhuman primates. This may help to achieve longer graft survival.

First data from a commercial local electrode atom probe (LEAP).

The first dedicated local electrode atom probes (LEAP [a trademark of Imago Scientific Instruments Corporation]) have been built and tested as commercial prototypes. Several key performance parameters have been markedly improved relative to conventional three-dimensional atom probe (3DAP) designs. The Imago LEAP can operate at a sustained data collection rate of 1 million atoms/minute. This is some 600 times faster than the next fastest atom probe and large images can be collected in less than 1 h that otherwise would take many days. The field of view of the Imago LEAP is about 40 times larger than conventional 3DAPs. This makes it possible to analyze regions that are about 100 nm diameter by 100 nm deep containing on the order of 50 to 100 million atoms with this instrument. Several example applications that illustrate the advantages of the LEAP for materials analysis are presented.

Patient-controlled analgesia.

This overview has addressed some of the key principles relating to patient-controlled analgesia. It is important to remember that PCA will continue to develop in the future and new techniques are being devised. PCA can provide an effective method of analgesia for many patients. However, it is not the only form of analgesia available, therefore a thorough assessment must be made before starting to use this analgesic technique.

Functional evaluation of the medtronic stentless porcine xenograft mitral valve in sheep.

BACKGROUND: Recently, renewed interest in allograft and stentless "freehand" bileaflet xenograft mitral valve replacement has arisen. The variability of human papillary tip anatomy and scarcity of donors limit allograft availability, making xenograft mitral valves an attractive alternative; however, these valves require new surgical implantation techniques, and assessment of their hemodynamics and functional geometry is lacking. METHODS: Seven sheep underwent implantation of a new stentless, glutaraldehyde-preserved porcine mitral valve (Physiological Mitral Valve [PMV], Medtronic) and were studied acutely under open-chest conditions. A new method of retrograde cardioplegia was developed. Hemodynamic valve function was assessed by epicardial Doppler echocardiography. 3D motion of miniature radiopaque markers sutured to the valve leaflets, annulus, and papillary tips was measured. Six other sheep with implanted markers served as controls. RESULTS: Both papillary muscle tips avulsed in the first animal, leaving 6 other animals. Mitral regurgitation was not observed in any xenograft valve. The peak and mean transvalvular gradients were 4.6+/-1.8 mm Hg and 2.6+/-1.5 mm Hg, respectively. The average mitral valve area was 5.7+/-1.6 cm(2). Valve closure in the xenograft group occurred later (30+/-11 ms, P<0. 015) and at higher left-ventricular pressure (61+/-9 mm Hg, P<0.001) than in the control group; furthermore, leaflet coaptation was displaced more apically (5.6+/-2.2 mm, P<0.001) and septally (5. 8+/-1.5 mm, P<0.001), and the anterolateral papillary tip underwent greater septal-lateral displacement (2.7+/-1.5 mm, P<0.001). Annular contraction during the cardiac cycle was similar in the 2 groups (xenograft 9.2+/-4.5% versus control 10.6+/-4.5% [mean+/-SD; 2-factor ANOVA model]). CONCLUSIONS: Successful freehand stentless porcine mitral valve implantation is feasible in sheep and was associated with excellent early postoperative hemodynamics. Physiological mitral valve annular contraction and functional leaflet closure mechanics were preserved. Long-term valve durability, calcification, and hemodynamic performance remain to be determined in models.

Most ovine mitral annular three-dimensional size reduction occurs before ventricular systole and is abolished with ventricular pacing.

BACKGROUND: Conventional surgical thinking indicates that mitral annular (MA) size reduction plays a key role in mitral valve closure, and most MA size and shape changes are thought to occur during left ventricular (LV) systole. The influences of left atrial (LA) and LV systole on MA size and shape, however, remain debated. METHODS AND RESULTS: Eight radiopaque markers were placed equidistantly around the MA and imaged using high-speed simultaneous biplane videofluoroscopy in seven closed-chest, sedated sheep before and during asynchronous LV pacing. Marker images were used to compute the three-dimensional coordinates of each marker every 16.7 ms throughout the cardiac cycle, allowing calculation of three-dimensional MA area, septal-lateral (SL) dimension, and commissure-commissure (CC) dimension under control and LV pacing conditions. Maximum MA area occurred in early diastole, and minimum MA area near end-diastole; maximum area reduction was 12+/-1% (P< or =.001). Interestingly, 89+/-3% of area reduction occurred before LV systole. During this "presystolic" period, SL decreased by 8+/-1% and CC by 2+/-1%; the SL/CC ratio fell from 0.73+/-0.02 to 0.69+/-0.01 (P< or =.005), indicating a less circular shape at end-diastole. With LV pacing, total MA area reduction was similar (13+/-2 versus 12+/-1%, P=NS versus control); however, all MA area reduction occurred during LV systole with minimum MA area occurring at end-systole. Presystolic shortening in both SL and CC dimensions was lost, and presystolic ellipticalization disappeared. CONCLUSIONS: Changes in MA size and shape coincident with LA systole included area reduction and shape change prior to the onset of LV contraction. These presystolic changes vanished when LA systole was absent (LV pacing). Thus, LA systole plays a pivotal role in MA size reduction and shape alteration. The unexpected timing of these MA dynamics should be taken into account during mitral valve reparative procedures.

Exploring better methods to preserve the chordae tendineae during mitral valve replacement.

BACKGROUND: It is not known how best to resuspend the mitral chordae tendineae during mitral valve replacement to optimize postoperative left ventricular (LV) systolic and diastolic function. METHODS: Six different techniques to preserve the chordae during mitral valve replacement were compared in 12 dogs using a nondistorting isovolumic technique: conventional, all chordae severed; anterior, all chordae preserved anteriorly; partial, anterior papillary muscle chordae preserved anteriorly; posterior, all chordae preserved posteriorly; oblique, anterior papillary muscle chordae directed anteriorly and posterior papillary muscle chordae posteriorly; and counter, opposite of oblique chordal direction. Control measurements (no chordal tension) were recorded between each experimental condition. RESULTS: The oblique method tended to have the best LV systolic function versus the conventional method (Emax = 4.0 +/- 1.8 versus 3.3 +/- 1.2 mm Hg/mL [mean +/- standard deviation]; p = 0.08 by repeated-measures analysis of variance; physiologic intercept Ees100 = 20.3 +/- 8.6 mL [p < 0.05 versus control]), with no major change in LV diastolic stiffness. The posterior method had a lower Emax (3.3 +/- 1.2 mm Hg/mL) than the oblique method, but a similar Ees100 (20.8 +/-8.1 mL; p < 0.05 versus control) and the best diastolic LV performance (LV diastolic stiffness = 0.46 +/- 0.23 mm Hg/mL). The counter method also had good systolic function (Emax = 3.8 +/- 1.2 mm Hg/mL; Ees100 = 19.7 +/- 7.5 mL; p < 0.05 versus control), but had less favorable diastolic properties (0.65 +/- 0.37 mm Hg/mL; p < 0.05 by repeated-measures analysis of variance versus posterior). CONCLUSIONS: In this isovolumic preparation in normal canine hearts, the oblique method of chordal resuspension was associated with the best LV systolic function, whereas the counter technique impaired LV diastolic function. These preliminary results warrant further study in ejecting and failing hearts to determine conclusively which chordal orientation best preserves LV performance after mitral valve replacement.

Pitfalls in creation of left atrial pressure-area relationships with automated border detection.

Creation of pressure-area relationships (loops) with automated border detection (ABD) involves correction for the variable inherent delay in the ABD signal relative to the pressure recording. This article summarizes (1) the results of in vitro experiments performed to define the range of, and factors that might influence, the ABD delay; (2) the difficulties encountered in evaluating a thin-walled structure like the left atrium in the dog model; and (3) the solutions to some of the difficulties found. The in vitro experiments showed that the ABD delay relative to high-fidelity pressure recordings ranges from 20 to 34 msec and 35 to 57 msec at echocardiographic frame rates of 60/sec and 33/sec, respectively. The delay was not influenced significantly by the type of transducer used, distance from the target area, or size of the target area. The delay in the ABD signal, relative to the echocardiographic image, ranges from nil to less than one frame duration, whereas it is delayed one to two frame durations relative to the electrocardiogram processed by the imaging system. In the dog model, inclusion of even small areas outside the left atrium rendered curves with apparent physiologic contour but inappropriately long delays of 90 to 130 msec. To exclude areas outside the left atrial cavity, time-gain compensation and lateral gain compensation were used much more extensively than during left ventricular ABD recording. By changing the type of sonomicrometers used in our experiments, we were able to record simultaneously ABD and ultrasonic crystal data. However, both spontaneous contrast originating from a right-sided heart bypass pump and electronic noise from the eletrocautery severely interferred with ABD recording.

Rigid ring fixation of the mitral annulus does not impair left ventricular systolic function in the normal canine heart.

BACKGROUND: Previous studies suggest that rigid fixation of the mitral annulus with an annuloplasty ring may impair left ventricular (LV) systolic performance. We used load-insensitive indexes of global and regional LV contractile mechanics to test the hypothesis that rigid fixation of the mitral annulus alters LV systolic function. METHODS AND RESULTS: Global and regional LV systolic mechanics were compared in 10 dogs during two mitral annular conditions: rigidly fixed and freely mobile. Carpentier-Edwards annuloplasty rings (20-24 mm) were inserted using a special buttressing suture technique that permitted alternate cinching of the ring down onto the annulus and subsequent removal away from the annulus. Aortic flow was measured with an electromagnetic flow probe, LV pressure by a micromanometer, and LV wall thickness and three near-orthogonal LV endocardial chamber dimensions using piezoelectric crystals during four sequential ring conditions: 1) down, 2) away, 3) down, and 4) away. The following parameters were analyzed during each ring condition to assess global LV systolic function: end-systolic chamber elastance (end-systolic pressure-volume relation), fiber elastance (end-systolic stress-volume relation), preload recruitable stroke work, and myocardial stress-strain relation. Additionally, regional LV systolic performance was assessed using the end-systolic pressure-diameter relation and a regional analog of preload recruitable stroke work. No significant differences in any of these measurements of LV systolic mechanics were observed between the two mitral annular conditions. CONCLUSIONS: Rigid fixation of the mitral annulus alters neither global nor regional LV systolic function in anesthetized, open-chest dogs with normal ventricles.

Ultrasonic tissue characterization with a real time integrated backscatter imaging system in normal and aging human hearts.

Experimental studies have shown that variation in the magnitude of integrated ultrasonic backscatter during the cardiac cycle represents acoustic properties of myocardium that are affected by pathologic processes; however, there are few clinical studies using integrated backscatter. Forty subjects without cardiovascular disease (aged 22 to 71 years, mean 41) were studied with use of a new M-mode format integrated backscatter imaging system to characterize the range of cyclic variation of integrated backscatter in normal subjects. Cyclic variation in integrated backscatter was noted in both the septum and the posterior wall in all subjects. The magnitude of the cyclic variation of integrated backscatter and the interval from the onset of the QRS wave of the electrocardiogram to the minimal integrated backscatter value were measured using an area of interest of variable size for integrated backscatter sampling and a software resident in the ultrasound scanner. The magnitude of cyclic variation was larger for the posterior wall than for the septum (6.3 +/- 0.8 versus 4.9 +/- 1.3 dB, p less than 0.01). The interval to the minimal integrated backscatter value was 328 +/- 58 ms for the septum and 348 +/- 42 ms for the posterior wall (p = NS). There was a weak correlation between the magnitude of cyclic variation of integrated backscatter and subject age for the posterior wall (r = -0.47, p less than 0.01), but this was not significant for the septum (r = -0.21) (partially because of inability to exclude specular septal echoes) and septal endocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic contrast increases the yield for right ventricular pressure measurement by Doppler echocardiography.

Doppler ultrasound has become accepted as a measurement of right ventricular systolic pressure in patients who have a quantifiable signal from tricuspid regurgitation. This study evaluated the use of intravenous injection of saline solution for echo contrast to increase the percentage of quantifiable tricuspid regurgitant signals in patients who have any detectable tricuspid regurgitation at baseline. Patients underwent a standard Doppler evaluation, followed by a contrast study with the injection of 4 to 6 ml of agitated saline solution into a brachial vein. Baseline and contrast tricuspid regurgitant signals were assessed for quality, quantifiability, and reproducibility of the derived pressures by three observers on two occasions. The average absolute pairwise deviation among the three observers was low: 1.6 mm Hg (standard deviation, 1.4 mm Hg). The intraobserver mean discrepancy was low: 0.03 mm Hg (standard deviation, 2.33 mm Hg). Patients who did not have tricuspid regurgitation (n = 10) failed to develop such regurgitation during contrast injection. Only eight of 40 patients (20%) who had trace or mild tricuspid regurgitation had quantifiable baseline signals, but 34 patients (85%) had quantifiable signals with contrast injection. All patients who had mild to moderate, moderate, or severe tricuspid regurgitation (n = 10) had quantifiable signals before contrast injection. Of all patients who had any tricuspid regurgitation, 88% had quantifiable signals with contrast injection. Echo contrast was shown to improve the yield of quantifiable signals in patients who had trace and mild tricuspid.

Ultrasonic tissue characterization of human hypertrophied hearts in vivo with cardiac cycle-dependent variation in integrated backscatter.

Integrated ultrasonic backscatter (IB) is a noninvasive measure of the acoustic properties of myocardium. Previous experimental studies have indicated that altered acoustic properties of the myocardium are reflected by the magnitude of variation of IB during the cardiac cycle. In our study, cardiac cycle-dependent variation of IB was noninvasively measured using a quantitative IB imaging system in 12 patients with uncomplicated pressure-overload hypertrophy and 13 patients with hypertrophic cardiomyopathy. Sixteen normal subjects served as a control. The magnitude of cardiac cycle-dependent variation of IB for the posterior wall was 6.0 +/- 0.9 dB in normal subjects, 5.7 +/- 0.8 dB in the patients with uncomplicated pressure-overload hypertrophy, and 6.7 +/- 2.1 dB in the patients with hypertrophic cardiomyopathy. There were no significant differences among any of these groups. In contrast, the magnitude of cardiac cycle-dependent variation of IB for the septum was significantly smaller in the patients with uncomplicated pressure-overload hypertrophy (2.8 +/- 1.3 dB) and in the patients with hypertrophic cardiomyopathy (3.1 +/- 2.3 dB) than in normal subjects (4.9 +/- 1.0 dB). The magnitude of cardiac cycle-dependent variation of IB was smaller as the wall-thickness index increased (r = -0.53, p less than 0.01, n = 82 for all data). This IB measure also correlated with percent-systolic thickening of the myocardium (r = 0.67, p less than 0.01, n = 82). Thus, alteration in the magnitude of cardiac cycle-dependent variation of IB was observed in hypertrophic hearts and showed apparent regional myocardial differences.

Mitral prosthesis malfunction. Comparative Doppler echocardiographic studies of mitral prostheses before and after replacement.

To assess the influence of mitral prosthesis malfunction on various Doppler echocardiographic indexes, we studied the changes in the peak mitral flow velocity during early diastolic filling phase (Vmax), the mean transprosthesis pressure drop from the simplified Bernoulli equation, the mitral valve area by the pressure half-time method, and the left ventricular isovolumic relaxation time in 15 patients before and after replacement of the malfunctioning mitral prosthesis using continuous wave Doppler echocardiography. Examination of the 15 replaced prostheses revealed a torn or perforated leaflet in 12 valves and a sewing ring dehiscence in one valve. Additional restricted leaflet motion (classified as mild obstruction) was seen in three of these 13 valves. In the remaining two valves, severe prosthesis obstruction was noted. Changes in the Doppler indexes between the preoperative and postoperative study were present in all patients regarding Vmax (mean, 2.2 +/- 0.3 versus 1.6 +/- 0.2 m/sec; p less than 0.001), mean gradient (mean, 9 +/- 5 versus 5 +/- 0.8 mm Hg; p less than 0.001), and isovolumic relaxation time (mean, 47 +/- 12 msec versus 80 +/- 13 msec; p less than 0.001). The mean mitral valve area remained virtually unchanged (2.3 +/- 0.9 versus 2.6 +/- 0.3 cm2; p = NS) but increased postoperatively in each patient with preoperative mild or severe prosthesis obstruction without concomitant aortic regurgitation. Our conclusion is that the peak mitral flow velocity, the mean gradient, and the isovolumic relaxation time are useful parameters in the differentiation of normal and abnormal mitral prosthesis function but may not define the underlying lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipomatous hypertrophy of the interatrial septum: characterization by transesophageal and transthoracic echocardiography, magnetic resonance imaging, and computed tomography.

Lipomatous hypertrophy of the interatrial septum is a benign condition that must be distinguished from other space-occupying lesions of the atria. Patients with this disorder generally have chronic pulmonary disease and thus are difficult to image with conventional transthoracic two-dimensional echocardiography. Transesophageal echocardiography can provide high quality imaging of intracardiac structures in patients who lack adequate transthoracic echocardiographic windows as a result of pulmonary disease. This case report describes the appearance of lipomatous hypertrophy of the interatrial septum as investigated by transesophageal echocardiography.

Transesophageal two-dimensional echocardiography and color Doppler flow velocity mapping in the evaluation of cardiac valve prostheses.

To determine the value of transesophageal ultrasound in the assessment of cardiac valve prostheses, 14 patients with clinically suspected mitral prosthesis malfunction were studied by transthoracic and transesophageal two-dimensional imaging as well as by color Doppler flow velocity mapping (color Doppler). Patients underwent left ventricular angiography (n = 13), surgery (n = 11), or both angiography and surgery (n = 10). Nine patients had only mitral valve replacement, four patients had both mitral and aortic valve replacement, and one patient had mitral, aortic, and tricuspid valve replacement. There were 16 biological and four mechanical prostheses. The degree of mitral regurgitation was graded by both transthoracic and transesophageal color Doppler according to the area of the regurgitant jet visualized and was compared with a three-point classification of mitral regurgitation by left ventricular angiography judged by observers blinded to the echocardiographic results. All transesophageal studies were performed without complication and were well tolerated. The pathological morphology of the mitral prosthesis was additionally or more clearly visualized by transesophageal two-dimensional imaging and subsequently proven at surgery in three patients with flail leaflets and one patient with a vegetation compared with images obtained by the transthoracic approach. Valvular regurgitation was graded by the transthoracic approach as absent in four patients, mild in two patients, moderate in five patients, and severe in only three patients. The transesophageal assessment showed absence of mitral regurgitation in two patients, moderate regurgitation in two patients, and severe regurgitation in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of avian aflatoxicosis on the synthesis of polyamines.

Effects were examined of inanition, dietary aflatoxin (2.5 mg/kg), and dietary supplements of threonine, lysine, and arginine on the activities of renal arginase and hepatic ornithine decarboxylase and on the accumulation of polyamines in liver and brain of 24 or 26-day-old broiler cockerels. Aflatoxicosis and inanition lowered the activity of renal arginase by 58 and 37%, respectively. Supplemental dietary threonine (.4%) did not suppress the activity of renal arginase, while fortification of diets of controls with lysine (.53%), but not diets containing aflatoxin, elevated the activity of renal arginase. Supplements of dietary lysine and/or arginine did not influence the hepatic content of putrescine but lowered the concentrations of spermidine and spermine. Aflatoxicosis, but not inanition, increased the activity of hepatic ornithine decarboxylase (ODC; 22-fold), increased hepatic concentrations of putrescine and spermidine, but decreased spermine concentrations. The elevation of hepatic ODC, putrescine, and the ratio of spermidine to spermine parallels the enlargement of the liver caused by aflatoxicosis. Cadaverine and putrescine were not detected in avian brain, while cerebral concentrations of spermidine and spermine were not altered by aflatoxin, inanition, or by supplements of dietary lysine, arginine, or both lysine and arginine.