Serial changes during acute cardiac allograft rejection: quantitative ultrasound tissue analysis versus myocardial histologic findings

OBJECTIVES: The aim of this study was to assess 1) whether quantitative ultrasound tissue analysis by serial measurements of myocardial echo amplitudes can detect and monitor the onset and degree of acute cardiac rejection, as well as its resolution of acute rejection during treatment, and 2) whether changes in myocardial echo amplitudes are modified by repeat additional rejection episodes. BACKGROUND: Previous experimental studies, all involving heterotopic heart transplantation, have consistently shown reproducible alterations in myocardial echo amplitude during acute rejection episodes untreated by immunosuppressive agents. METHODS: Two-dimensional echocardiographic long-axis views were obtained daily under strict standardization in 12 dogs after heterotopic cervical heart transplantation (mean survival time 16.1 days) and digitized into a 256 x 256 x 8 matrix. Myocardial echo amplitudes were analyzed by gray level histogram statistics in regions of interest (45 x 12 pixels) within the proximal septum and posterior wall and correlated with the results of daily transmural myocardial biopsies. Maintenance immunosuppressive therapy consisted of cyclosporine, azathioprine and steroids. Additive steroids were given during acute cardiac rejection. RESULTS: All dogs experienced at least one moderate or severe episode of acute cardiac rejection. Successful resolution and repeat acute rejection were observed in three dogs. On 65 days, the left ventricular biopsy specimens showed no evidence of acute rejection. Mild acute rejection was present on 36, moderate on 29 and severe rejection on 40 days. End-diastolic mean (+/- SD) gray level increased progressively from 100.7 +/- 20.4 for no acute cardiac rejection to 113.8 +/- 23.1 for mild rejection (p = NS vs. no rejection) to 126.0 +/- 16.1 for moderate rejection (p < 0.01) and to 136.3 +/- 12.6 for severe rejection (p < 0.01). In each individual dog, a correlation between daily measurements of mean gray levels and histologic cardiac rejection grades was found (rmean = 0.80 +/- 0.14 [range 0.57 to 0.97], n = 12). In three dogs with transient complete histologic resolution of acute cardiac rejection, mean gray level did not return to values before rejection (108.0 +/- 15.4 vs. 87.2 +/- 8.4). The subsequent second episode of rejection was characterized by higher gray level values than those associated with the first rejection episode (141.3 +/- 14.4 vs. 124.3 +/- 20.9). CONCLUSIONS: Acute cardiac rejection is associated with a progressive increase in mean gray level. Changes in myocardial echo amplitudes in individuals may thus prove a useful tool for the noninvasive detection and monitoring of acute rejection. Increased mean gray level values after resolution of rejection may indicate persistent structural tissue abnormalities after rejection and demonstrate the need to define new baseline values after histologic resolution of an acute rejection episode.     

Effect of dietary lipids on hepatic and extrahepatic sterol 27-hydroxylase activity in high- and low-responding baboons

The aim of this study was to assess a Doppler-echocardiographic parameter which has not been previously reported for the diagnosis of acute cardiac rejection. The parameter was left ventricular isovolumic relaxation blood flow. Eighty patients who had undergone orthoptic cardiac transplantation were followed up regularly with echocardiography for a period of 2 years. In all, 495 echocardiographic studies were performed and the results compared with those of endomyocardial biopsy performed on the same day (11.4 echocardiographic studies per patient). In the absence of cardiac rejection, isovolumic relaxation Doppler signal was recorded in all patients (364/387 echo studies). This was a positive signal directed towards the apex detected by continuous mode Doppler in the apical position, arising along the interventricular septum in the mid part of the left ventricle (82% of cases) or from the basal region of the septum (18% of cases) and lasting throughout the phase of isovolumic relaxation. The maximal velocity was 0.53 +/- 0.08 m/s (range 0.32 to 0.73 m/s) : the velocity-time integral was 34 +/- 33 cm. This signal was associated with medioventricular endosystolic acceleration of blood flow in 75% of cases. The incidence of the isovolumic relaxation flow signal decreased in cardiac rejection with no significant changes in the other usual Doppler-echocardiographic parameters except for a significant decrease in the ejection fraction in the group with severe rejection. In the group with mild rejection (n = 89) an isovolumic relaxation flow signal was only observed in 52 cases (including 29 in whom immunosuppressive treatment was not increased). In patients with moderate rejection (n = 12) there were only 5 cases in which a isovolumic relaxation flow signal was recorded, and in the group with severe rejection (n = 7), the signal could only be recorded in 1 case. The authors conclude that the absence of an isovolumic relaxation blood flow signal in a cardiac transplant patient is a reliable sign of cardiac rejection with an excellent specificity (94%). The absence of this signal is a sensitive indicator of severe rejection (86%) but less so for moderate (58%) or mild rejection (42%).     

Increased myocardial echo density in left ventricular pressure and volume overload in human aortic valvular disease: an ultrasonic tissue characterization study

Quantitatively assessed ultrasonic backscatter is an index of ultrasonic tissue characterization directly related to morphometrically evaluated collagen in human beings. Our objective was to assess myocardial reflectivity pattern of patients with severe left ventricular hypertrophy caused by either aortic stenosis (AS) or aortic regurgitation (AR). Ten patients with AS, 10 patients with AR, and 10 closely age- and gender-matched healthy controls were studied by two-dimensional Doppler echocardiography. By using an echocardiographic prototype, we performed a radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and the posterior wall (integrated backscatter index: IBI, expressed in percentage). All patients with stenosis or aortic insufficiency showed a normal regional and global resting systolic function (fractional shortening: AS = 36.0 +/- 6.6 versus AR = 40.3 +/- 6.2 versus control = 40.2 +/- 8.7; p = not significant [NS]) Left ventricular mass index (Devereux's formula) was markedly increased in patients with stenosis or aortic insufficiency (AS = 199.3 +/- 18 versus AR = 208.8 +/- 60 versus control = 97.3 +/- 11 g/m2; p < 0.0001). Myocardial echo density was increased in patients with stenosis or aortic insufficiency in comparison with controls, both in the septum (IBI%: AR = 40.7 +/- 7.9 versus AS = 33.4 +/- 4.2 versus control = 23.0 +/- 6.2; p < 0.0001) and in the posterior wall (IBI%: AR = 27.1 +/- 4.3 versus AS = 23.0 +/- 2.6 versus control = 15.0 +/- 4.2; p < 0.0001). No significant correlations were found between septal and posterior wall IBI and their thickness. Abnormally increased myocardial echo density--possibly related to disproportionate collagen deposition--can be detected in patients with pressure or volume overload caused by aortic valve disease and without overt systolic dysfunction.     

Myocarditis in children with dilated cardiomyopathy: incidence and outcome after dual therapy immunosuppression

BACKGROUND: The true incidence and prognosis of myocarditis in children with acute dilated cardiomyopathy (DCM) at presentation remains uncertain. This study examines the incidence of lymphocytic myocarditis in a consecutive cohort of children with acute DCM at presentation and outcome after dual therapy immunosuppression with cyclosporine and steroids. METHODS: Twenty-nine consecutive children with acute DCM underwent early endomyocardial biopsy. Children with "definite" myocarditis comprised group I (n = 9) and were treated with cyclosporine and prednisolone. Group II (n = 2) had "borderline" myocarditis, and group III (n = 18) nonspecific histologic findings. Outcome was assessed by echocardiographic measurement of left ventricular end-diastolic dimension and fractional shortening, with follow-up endomyocardial biopsy in group I subjects. RESULTS: Myocardial inflammation with or without myocardial necrosis (groups I and II) was present in 38% of all cases. There were no initial clinical, electrocardiographic, or echocardiographic features to distinguish patients in group I from patients in group III. At presentation, the mean +/- SEM left ventricular end-diastolic dimension and fractional score-Z scores of group I patients were 4.6 +/- 1.7 and -5.1 +/- 0.8, respectively, compared with 0.8 +/- 0.3 and -0.9 +/- 0.4, respectively, at withdrawal of immunosuppression (p < 0.001 for both). Both of these parameters did not differ significantly from normal controls at least follow up. Two group I patients had a biopsy-proven relapse after withdrawal of therapy that responded to reinstitution of immunosuppression. At latest follow-up, all nine group I patients had regained normal left ventricular function compared with four of 18 group III patients (p < 0.001). CONCLUSION: Lymphocytic myocarditis is frequent in children with dilated cardiomyopathy and cannot be predicted from noninvasive investigations. The use of cyclosporine and steroids is associated with a favorable outcome, and a controlled trial of dual therapy immunosuppression in children is therefore warranted.     

Heterodimerization is mainly responsible for the dominant negative activity of amino-terminally truncated rat androgen receptor forms

BACKGROUND: Previous reports investigating the clinical course and management of inflammatory bowel disease (IBD) after orthotopic liver transplant (OLT) have revealed conflicting results. METHODS: To determine the natural history and course of therapy for liver transplant patients with IBD, we reviewed the records of 35 patients, who underwent OLT between 1985 and 1996 and who had a history of either IBD (29 patients) or primary sclerosing cholangitis (PSC) without evidence of IBD before OLT (6 patients). Of 29 patients with IBD before OLT, 25 had a history of ulcerative colitis (UC) and 4 had Crohn's disease. Six patients had undergone total colectomy, one subtotal colectomy, and three partial colectomy before OLT. Mean follow-up after OLT was 37+/-6.4 months. Immunosuppression included cyclosporine, prednisone, and azathioprine in 34 patients and tacrolimus and prednisone in 1 patient. RESULTS: After OLT, 17 patients (49%) had quiescent disease and were receiving no additional medications other than standard immunosuppression to prevent organ rejection. Five patients (14%) had mild flares controlled with initiation of 5'-aminosalicylates (5'-ASA), and two patients (6%) required an increase in oral prednisone. Only one patient with PSC, without evidence of IBD before OLT, developed IBD after OLT. No patients required intravenous steroids or surgical intervention for active IBD. CONCLUSIONS: (1) Standard postOLT immunosuppressive agents in patients undergoing OLT with IBD were able to adequately control disease activity after OLT in the majority of patients. (2) IBD flares after OLT were generally well controlled with aminosalicylates or oral steroids. (3) Aminosalicylates were helpful in the clinical management of IBD, even when patients were taking standard doses of steroids, azathioprine, and cyclosporine.     

Detection of acute rejection of heart transplantation by Doppler color imaging

Doppler tissue imaging is a new technique of measuring the velocities of myocardial wall motion. In order to assess its value in the diagnosis of acute rejection, the velocities of the interventricular septum and left ventricular posterior wall were measured in systole and early diastole in 34 cardiac transplant patients at the time of their endomyocardial biopsy, using an M mode left parasternal short axis view. During 40 episodes of acute rejection (26 mild and/or moderate, 10 sub-severe and 4 severe), the wall velocities decreased significantly (p < 0.001) both in the interventricular septum and endocardium of the posterior wall. Myocardial velocities were significantly slower in sub-severe or severe rejection than in mild or moderate rejection. The most sensitive criterion was the measurement of posterior wall endocardial velocity in early diastole, a decrease of 10% having a sensitivity of 92% whereas the sensitivity of usual Doppler echocardiographic parameters is only 73%. Acute rejection, even mild cases, can be diagnosed with excellent sensitivity by measuring myocardial velocities by Doppler tissue imaging. This technique has the advantage of being non-invasive, reproducible and reliable in the follow-up of cardiac transplant patients.     

Comparison of myocardial velocities by tissue color Doppler imaging in normal subjects and in dilated cardiomyopathy

The authors studied 35 normal subjects (41 +/- 6 years) and 22 patients with idiopathic dilated cardiomyopathy 48 +/- 7 years; ejection fraction: 31 +/- 12%) in order to determine normal values of myocardial velocities and to demonstrate the sensitivity of Doppler tissue imaging in detecting a significant decrease in myocardial velocities in patients with abnormal left ventricular contractility. Interventricular septal and left ventricular posterior wall velocities were recorded by M mode long axis parasternal views. In normal subjects, a velocity gradient in the posterior wall was observed, higher in the endocardium than in epicardium, in systole (5.1 +/- 1.5 versus 2.8 +/- 1 cm/s, p < 0.01), and early diastole (13.7 +/- 3.5 versus 5.7 +/- 2 cm/s, p < 0.001) and late diastole at the time of atrial contraction (2.7 +/- 2.1 versus 1.8 +/- 1.7 cm/s, p < 0.01). Moreover, the velocities are higher in the posterior wall than in the interventricular septum throughout the cardiac cycle. Finally, the velocities are higher in early diastole than in systole, both in the interventricular septum and posterior wall. In the group of patients with idiopathic dilated cardiomyopathy, the intramyocardial velocities were lower than in normal subjects. In addition, the velocity gradient in the posterior wall was absent in 15 of the 22 patients. The authors conclude that Doppler tissue imaging provides new information in the analysis of myocardial function both in systole and diastole.     

Candida glabrata prosthesis infection following pyelonephritis and septicaemia

A 48-year-old woman with no cardiovascular risk factors was admitted to the hospital because of acute dyspnea. At 27-year-old, she developed Hodgkin's disease, that was successfully treated with splenectomy, combined chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone-MOPP regimen) and radiotherapy (4500 rads). At 43-year-old the lymphoma relapsed and she had further chemotherapy with doxorubicin, bleomycin, vinblastina and dacarbazine. After this treatment, she had an episode of pulmonary edema, attributed to doxorubicin acute cardiotoxicity. She responded to digitalis and diuretics and was discharged with an electrocardiogram (ECG) showing left bundle branch block and a normal echocardiogram. The patient enjoyed good health for several years and 4 months before the present admission the ECG and echocardiogram were unchanged. On this admission there were signs of left ventricular failure with acute pulmonary edema, and a new soft apical murmur (3-4 Levine). The patient required endotracheal intubation and high doses of diuretics, digitalis and vasodilators. The cardiac enzymes were negative, the serial ECGs confirmed left bundle branch block, while the echocardiogram showed moderate to severe mitral regurgitation, akinesia of the interventricular septum and inferior wall with dilation of the left ventricle. A previous silent myocardial infarction was suspected. After recovery, she underwent cardiac catheterization confirming akinesia of the interventricular septum and inferior wall with moderate mitral regurgitation, while coronary angiography showed a critical ostial stenosis of the right coronary artery. In view of a dipyridamole-thallium scan negative for myocardial viability, reperfusion was not attempted. With changes in radiotherapeutic techniques, the incidence of radiation-induced heart disease (pericarditis, myocarditis, conduction abnormalities and, rarely, occlusive coronary artery disease) is declining. Nevertheless, after irradiation of the chest and mediastinum a longterm cardiological follow-up is useful in selecting patients at higher risk of radiation-induced coronary artery disease, who will eventually require coronary angiography and reperfusion intervention.     

Protein-nucleic acid interactions and DNA conformation in a complex of human immunodeficiency virus type 1 reverse transcriptase with a double-stranded DNA template-primer

Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using 18F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the inter-ventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6 +/- 1.6 vs. 4.1 +/- 0.5, p < 0.01) and posterolateral wall (5.9 +/- 0.7 vs. 3.8 +/- 0.5, p < 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases.     

Early cardiac allograft rejection is independent of regional myocardial blood flow

Noninvasive telemetric monitoring of canine heterotopic cardiac allograft unipolar peak-to-peak amplitude (UPPA) has permitted prospective surveillance for rejection; moreover, this technique is able to reliably detect rejection before the development of histologic evidence of myocyte necrosis. This study was performed to determine whether early cardiac allograft rejection and the accompanying decline in allograft UPPA were associated with alterations in regional myocardial blood flow (RMBF). Seven heterotopic, intrathoracic canine cardiac transplantations were performed using triple-drug immunosuppression. Native hearts and allografts were instrumented with right ventricular and left ventricular epicardial screw-in electrodes connected to subcutaneous telemeters. Daily measurement of native and graft UPPA was performed; using radioactive microspheres, native and graft RMBF were determined during the control period and when UPPA had declined by 15%, 30%, and 45%. Graft histologic status was determined by endomyocardial biopsy at the time of RMBF determination. Mean duration of the study was 19.7 +/- 3.9 days. Rejection was documented in all animals. The UPPA was stable in native hearts; UPPA declined in the allografts after the onset of rejection. A biphasic change in allograft blood flow was seen. Initially RMBF increased as UPPA declined; a 30% to 45% reduction in UPPA was associated with a 41% increase in RMBF (p = 0.028 versus allograft control). Subsequently, a significant decline in blood flow was observed for reductions in UPPA greater than 45% (0.68 +/- 0.44 versus 1.07 +/- 0.47 mL.g-1 x min-1 for a 30% to 45% decline in UPPA; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prospective identification of ventricular septal defects in infancy using subxiphoid two-dimensional echocardiography

The objective of this study was to establish a dependable technique for imaging the interventricular septum and ventricular septal defects in infants. Subxiphoid two-dimensional echocardiograms were performed on 81 infants who were 1 day to 12 months (median 43 days) old and weighed 1.6-8.6 kg (median 3.4 kg). A short-focus, 5-MHz crystal with a 13-mm active element diameter was used in all studies. The interventricular septum was visualized in 80 of 81 infants. Defects in the membranous, atrioventricular canal, conoventricular and muscular segments of the sentum were identified using three standard transverse subxiphoid projections. All defects in the membranous and atrioventricular canal segments, as well as malalignment type conoventricular communications, were correctly identified when compared with selective angled cineangiocardiography. Only two of the three subpulmonic and four of 11 muscular defects were identified successfully. Limitations in imaging defects in the muscular septum reflected the varied morphology of these interventricular communications and the tangential orientation of the echo beam to the extreme apical and anterior segments of the muscular septum.     

Evaluation of biopsy classification for rejection: relation to detection of myocardial damage by monoclonal antimyosin antibody imaging

OBJECTIVES: This study sought to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global estimate of myocardial transplant-related cardiac damage detected by myocardial uptake of monoclonal antimyosin antibodies. BACKGROUND: The diagnosis and treatment of acute cardiac allograft rejection is based on the interpretation of endomyocardial biopsies. Because allograft rejection is a multifocal process and biopsy is obtained from a small area of the right ventricle, sampling error may occur. Global assessment of myocardial damage associated with graft rejection is now possible with the use of antimyosin scintigraphy. The present study was undertaken to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global assessment of transplant-related myocardial damage detected by antimyosin scintigraphy. METHODS: Biopsies (n=395) from 112 patients were independently interpreted by three pathologists in a blinded manner according to the original Stanford four-grade (normal, mild, moderate and severe) and the current International Society of Heart and Lung Transplantation (ISHLT) seven-grade (0, 1A, 1B, 2, 3A, 3B and 4) classifications. The results were correlated with 395 antimyosin studies performed at the time of the biopsies. The heart/lung ratio of antimyosin antibody uptake was used to assess the severity of myocardial damage. RESULTS: In the Stanford biopsy grade classification, significantly higher antimyosin uptake, indicating increasing degrees of myocardial damage, were associated with normal (1.78+/-0.26), mild (1.88+/-0.31) and moderate (1.95+/-0.38) biopsy classifications for rejection (p < 0.01). In the ISHLT classification, significant differences were detected only for antimyosin uptake associated with grades 0 (1.77+/-0.26) and 3A (1.98+/-0.39) but not for intermediate scores (1A, 1B and 2). In view of the similar intensity of antibody uptake among the various grades, ISHLT biopsy scores were regrouped: normal biopsies in grade A; 1A and 1B as grade B; and 2 and 3A as grade C. Antimyosin uptake in grades A, B and C was 1.78+/-0.26, 1.88+/-0.31, 1.95+/-0.38, respectively (p < 0.01). CONCLUSIONS: The current ISHLT seven-grade scoring system does not reflect the progressive severity of myocardial damage associated with heart transplant rejection. Because myocardial damage constitutes the basis of treatment for allograft rejection, there is a need to reevaluate the ISHLT grading system, given its importance for multicenter trials.     

Immediate reproducibility of upper limit of vulnerability measurements in patients undergoing transvenous implantable cardioverter defibrillator implantation

BACKGROUND: Asynchronous electrical activation, induced by ventricular pacing, causes regional differences in workload, which is lower in early- than in late-activated regions. Because the myocardium usually adapts its mass and structure to altered workload, we investigated whether ventricular pacing leads to inhomogeneous hypertrophy and whether such adaptation, if any, affects global left ventricular (LV) pump function. METHODS AND RESULTS: Eight dogs were paced at physiological heart rate for 6 months (AV sequential, AV interval 25 ms, ventricular electrode at the base of the LV free wall). Five dogs were sham operated and served as controls. Ventricular pacing increased QRS duration from 47.2+/-10.6 to 113+/-16.5 ms acutely and to 133.8+/-25.2 ms after 6 months. Two-dimensional echocardiographic measurements showed that LV cavity and wall volume increased significantly by 27+/-15% and 15+/-17%, respectively. The early-activated LV free wall became significantly (17+/-17%) thinner, whereas the late-activated septum thickened significantly (23+/-12%). Calculated sector volume did not change in the LV free wall but increased significantly in the septum by 39+/-13%. In paced animals, cardiomyocyte diameter was significantly (18+/-7%) larger in septum than in LV free wall, whereas myocardial collagen fraction was unchanged in both areas. LV pressure-volume analysis showed that ventricular pacing reduced LV function to a similar extent after 15 minutes and 6 months of pacing. CONCLUSIONS: Asynchronous activation induces asymmetrical hypertrophy and LV dilatation. Cardiac pump function is not affected by the adaptational processes. These data indicate that local cardiac load regulates local cardiac mass of both myocytes and collagen.     

Linking cell-fate specification to planar polarity: determination of the R3/R4 photoreceptors is a prerequisite for the interpretation of the Frizzled mediated polarity signal

Hypertensive cardiac hypertrophy is associated with the accumulation of collagen in the myocardial interstitium. Previous studies have demonstrated that this myocardial fibrosis accounts for impaired myocardial stiffness and ventricular dysfunction. Although cardiac fibroblasts are responsible for the synthesis of fibrillar collagen, the factors that regulate collagen synthesis in cardiac fibroblasts are not fully understood. We investigated the effects of angiotensin II on cardiac collagen synthesis in cardiac fibroblasts. Cardiac fibroblasts of 10 week old spontaneously hypertensive rats and age-matched Wistar-Kyoto rats were prepared and maintained in culture medium supplemented with 10% fetal calf serum. The expression of mRNA of the renin-angiotensin system (renin, angiotensinogen, angiotensin converting enzyme) was determined by using a ribonuclease protection assay. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats was 1.6 fold greater than that in the cell of Wistar-Kyoto rats. Angiotensin II stimulated collagen synthesis in cardiac fibroblasts in a dose-dependent manner. The responsiveness of collagen production to angiotensin II was significantly enhanced in cardiac fibroblasts from spontaneously hypertensive rats (100 nM angiotensin II resulted in 185 +/- 18% increase above basal levels, 185 +/- 18 versus 128 +/- 19% in Wistar-Kyoto rats p < 0.01). This effect was receptor-specific, because it was blocked by the competitive inhibitor saralasin and MK 954. These results indicate that collagen production was enhanced in cardiac fibroblasts from spontaneously hypertensive rats, that angiotensin II had a stimulatory effect on collagen synthesis in cardiac fibroblasts, and that cardiac fibroblasts from spontaneously hypertensive rats were hyper-responsive to stimulation by angiotensin II. Level of angiotensin and renin mRNA expressed in ventricles, and angiotensinogen mRNA expressed in fibroblasts from SHR were higher than those from WKY. These findings suggest that the cardiac renin-angiotensin system may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.     

Diagnosis of endocardial cushion defect with cross-sectional and M-mode scanning echocardiography. Differentiation from secundum atrial septal defect

Twelve cases of endocardial cushion defect were studied before and after operation with ultrasono-cardiotomography (tomography) cross-sectional echocardiography, two-dimensional echocardiography, B-scan echocardiography) and M-mode scan along a horizontal section of the heart. For comparison, 20 healthy subjects, 18 cases of mitral valvular disease, 4 cases of congestive cardiomyopathy, 1 case of partial anomalous pulmonary venous drainage, and 25 cases of atrial septal defect of secundum type were also examined with the same technique. In cases without cardiac malformation, the echo of the anterior mitral valve was usually continuous medially with that of the interatrial septum in the horizontal plane at the level of the membranous septum. This feature was clearly recorded in all cases with right heart enlargement. In ostium secundum atrial septal defect the echo of the anterior mitral valve continued into that of the interatrial septum. An echo interruption was shown, indicating the defect itself to be in the middle part of the interatrial septum. In all the cases of endocardial cushion defect which we examined discontinuity was shown between the echo of the anterior mitral valve and that of the interatrial septum. This discontinuity was interpreted as indicating the defect itself. The mitral valve ring echo was close to the basal end of that of the interventricular septum, possibly reflecting an abnormal attachment of the mitral valve. In all cases, after operation, the echo of the artificial interatrial septum was recorded, continuous with that of the anterior mitral valve. The features of the echocardiographic sweep from the anterior mitral valve to the interatrial septum were thus different in the three groups. These echocardiographic differences are thought to correspond to the anatomical differences between the normal, atrial septal defect of secundum type, and endocardial cushion defect, and are essential features differentiating them from each other.     

Heart transplantation in children and young adults: early and intermediate-term results

The purpose of this article is to report our short- and intermediate-term follow-up of cardiac transplantation for congenital heart disease and cardiomyopathy in children (age greater than 6 months), adolescents, and young adults. Thirty patients (ages 8 months to 24 years) with end-stage heart failure have undergone cardiac transplantation in our program: 12 (40%) for postoperative end-stage heart failure, 9 (30%) as primary treatment for congenital heart disease, 5 (17%) for dilated cardiomyopathy, and 4 (13%) for restrictive/hypertrophic cardiomyopathy. Nineteen patients (63%) had undergone prior operations; 4 patients received transplants for failed Fontan procedures. Induction therapy with antithymocyte therapy was used routinely, and long-term immunosuppression was by cyclosporine and azathioprine alone. Rejection surveillance/diagnosis was based on echocardiographic criteria. Posttransplantation follow-up ranges from 3 to 78 months. Operative mortality was 3.3% (1/30). No patients have been diagnosed with either accelerated allograft atherosclerosis or posttransplantation lymphoproliferative disease. We conclude that cardiac transplantation may be performed with excellent early and intermediate-term results.     

Multivariable feedback active structural acoustic control using adaptive piezoelectric sensoriactuators

Patients with malabsorption and histological findings consistent with celiac disease, who are unresponsive to gluten free diet, and in whom other causes of flat mucosa have been excluded, are considered to suffer from so called unclassified or refractory sprue. Although the true nature of this condition needs to be further elucidated, it is known to represent a difficult therapeutical problem with potentially fatal course. Herein, we report a patient with refractory sprue-like disease who after failing to respond to corticosteroids and TPN was in a critical condition. He responded promptly to cyclosporine and made a remarkable recovery. In contrast to previous reports, the cyclosporine treatment in this patient was pursued only for 1 month, whereupon the patient turned responsive to steroids. Subsequent treatment with azathioprine allowed corticosteroids to be reduced to a low maintenance dose and eventually all drugs could be discontinued without reappearance of symptoms. Cyclosporine therapy might be lifesaving in occasional patients with refractory sprue-like disease and it may result in reversal of steroid resistance. Moreover, azathioprine seems to have a steroid sparing effect in this setting. Short term immunosuppressive treatment may have an advantage of lower risk for drug related side effects.     

An echocardiographic study of the interventricular septum in constrictive pericarditis

Ten patients with constrictive pericarditis were studied echocardiographically with specific reference to inter-ventricular septal dynamics. Abnormal movement of the interventricular septum was present in 8 patients and consisted of flattening in systole and unusual posterior motion in diastole. The aetiology of this type of movement is at present unknown but may be related to restriction of normal cardiac rotational dynamics. The interventricular septum also showed diminished degree of thickening (mean 21-2%). The amplitude of excursion was generally at the upper limit of or greater than normal. Left ventricular posterior wall amplitude of excursion was normal. Flattening of left ventricular posterior wall diastolic movement was seen in 4 patients. Right ventricular end-diastolic dimension was slightly increased (1-2 to 1-7 cm/m2) in 5 of 8 patients with abnormal septal motion, but no haemodynamic evidence of diastolic volume overload was found. Posterior pericardial thickening was noted echocardiographically when posterior calcification was present. We conclude that the most common though non-specific feature of the echocardiogram in patients with constrictive pericarditis is abnormal septal motion. Flattening of left ventricular posterior wall diastolic movement, posterior pericardial thickening, and epicardial-pericardial separation may also occur.     

HLA-identity--long-term renal graft survival, acute vascular, chronic vascular, and acute interstitial rejection

The object is analysis of the impact of acute and chronic rejection on long-term function in HLA-identical renal transplants performed from 1967 to 1995 by the Saskatchewan Renal Transplant Unit. Forty-eight grafts in 46 patients were studied, of which 39 were first and nine second grafts. Forty-two were for primary and six for secondary renal disease. Thirty-five received azathioprine/prednisone prophylaxis, and 13 received cyclosporine/prednisone with/without azathioprine. Ten-year all graft actuarial survival was 84%, 10-year actuarial graft survival in patients with primary renal disease 90%, and with subsequent graft after first HLA graft failed 97.5%, for age-matched population 98.5% (P=NS). Overall death rate was 8.7% (4/46); in secondary renal disease patients 50% (3/6); in primary renal disease patients 2.5% (1/40, P=0.004). All (9/9) HLA-identical second grafts functioned. Acute rejection with azathioprine/prednisone prophylaxis occurred in 55% (9/17) of grafts treated with <6 pre-graft blood transfusions, with the same prophylaxis but >5 units in 12% (2/16, P=0.015), and with cyclosporine prophylaxis in 13% (2/15, P=0.021). Pulse steroids alone reversed all acute rejection. Grafts failed in 6.2% (3/48), all in primary renal disease patients and one from technical one noncompliance, and one chronic rejection. Graft cost/patient/year amortized over 9 years is $3,855 and comparable dialysis cost would be $35,650; cost for all patients on dialysis for 9 years would be $11,293,320 while comparable graft cost was 1,221,418, a savings of 89.2%. Our conclusions are that HLA-identity associates with the following: (1) a 10-year actuarial survival in primary renal disease that equals that of the age-matched population, (2) uniform success in repeat grafts, (3) virtual absence of chronic rejection despite a high incidence of acute rejection in azathioprine/prednisone grafts that (4) always reversed on pulse steroids, and (5) a cost reduction for grafting of 93.2% compared with dialysis therapy.     

Heart transplantation in Chagas' disease. 10 years after the initial experience

BACKGROUND: Heart transplantation (HT) as a therapeutic option for end-stage chronic Chagas' heart disease (CCHD) is controversial. Reactivation of Trypanosoma cruzi infection and recurrence of the disease in the allograft are likely to occur. Furthermore, active myocarditis has been reported to predispose patients to an increased incidence and severity of rejection. METHODS AND RESULTS: We prospectively investigated the long-term follow-up of 10 patients with CCHD who underwent HT. Immunosuppression was based on cyclosporine A and azathioprine. T cruzi reactivation was prevented with benzonidazole. Besides allograft rejection surveillance, T cruzi infection was monitored through blood tests, myocardial biopsies, and serological tests. Over a mean follow-up period of 34 +/- 38 months (range, 73 to 124 months), 7 patients are alive and in NYHA functional class I. Life expectancy was 78% for the second year and 65% for 10 years. Rejection was less frequent in chagasic than in age- and sex-matched control patients (mean +/- SD, 1.60 +/- 1.26 versus 5.70 +/- 1.89 episodes per patient, respectively; P = .0001); decreased severity of rejection was also observed (P = .006). T cruzi parasitemias detected on three occasions were successfully treated with benzonidazole. There were no signs of recurrence of the disease in the allograft. CONCLUSIONS: These results suggest an important role of HT in the treatment of CCHD. There was a low frequency of T cruzi infection reactivation and no signs of recurrence of the disease in the allograft. The surprisingly decreased rejection incidence and severity require further studies for elucidation.