Detection of cardiac allograft rejection and myocyte necrosis by monoclonal antibody to cardiac myosin.

Indium 111-labeled monoclonal antibody to cardiac myosin was examined for efficacy in the detection of cardiac graft rejection and rejection-related myocyte necrosis. Heterotopic heart transplants were performed in isogenic and allogenic groups of rats (n = 56). At selected intervals posttransplant, uptake of injected antibody in the donor and native hearts was determined by gamma scintillation scanning. Indium uptake was compared to histologic results graded for the severity of rejection and the presence of myocyte necrosis. The donor heart uptake of labeled antibody was significantly greater in both moderate rejection and severe rejection than in lesser degrees of rejection (P = 0.05). The donor/native heart antibody uptake ratio (AUR) in both severe and moderate rejection were significantly different from no or mild rejection (P = 0.05). In pooled grafts without myocyte necrosis, both the absolute donor heart antibody uptake and the donor/native heart AUR were significantly greater in grafts with moderate or severe rejection than in those with no or mild rejection (P less than 0.001). Among grafts with moderate or severe rejection, those with myocyte necrosis had greater donor heart antibody uptakes and greater donor/native heart AUR than grafts without myocyte necrosis (P less than 0.001). The grade of rejection and the presence of histologic myocyte necrosis appear to be closely related but independent variables, both of which influence antibody uptake. It is concluded that monoclonal antibody to cardiac myosin may be a useful noninvasive tool that could distinguish moderate or severe rejection from lesser degrees of rejection and that could detect the presence of myocyte necrosis.

Pathology of the heart in sudden cardiac death.

Clinical and pathologic changes in 87 patients who could not be resuscitated from an episode of sudden cardiovascular collapse are described and compared with observations from patients in the same community who were successfully resuscitated from ventricular fibrillation. Findings in patients who died suddenly generally did not differ when the patients were groups by electrocardiographic rhythm on arrival of the mobile coronary aid unit. The pathologic changes of acute thrombosis and recent myocardial infarction did not occur with sufficient frequency in the entire group to be considered causally related to the sudden collapse, occurring in 10 and 5 percent of cases, respectively. Although most patients had evidence of obstructive coronary disease and old myocardial infarction, 8 percent had no significant vascular disease, acute thrombosis, myocarditis or valve disease that might be implicated as a factor in sudden death. There was no relation between age and severity of obstructive coronary disease or frequency of old myocardial infarction in patients who died suddenly. Complete atherosclerotic occlusion in one or more coronary vessels occurred in 51 of 87 (59 percent) and old myocardial infarction in 48 of 87 (55 percent). Although the mean age of this autopsy population was similar to that of all patients in the community who have had ventricular fibrillation on arrival of the aid unit, the nonsurvivors had a greater incidence of myocardial infarction and symptomatic heart disease (73 of 87) than did survivors. Comparison of this autopsy group with persons from the community who were resuscitated from ventricular fibrillation and subsequently had coronary angiograms indicates that the severity of coronary stenosis does not distinguish between survivors and nonsurvivors of an episode of ventricular fibrillation and suggests that other factors influence the outcome of an episode of ventricular fibrillation.

Validation of a computerized QRS criterion for estimating myocardial infarction size and correlation with quantitative morphologic measurements.

This replication study describes the relation of myocardial infarction (MI) size, measured at autopsy, to initial and late QRS abnormalities, measured by computerized spatial vectorcardiography. Thirty-one patients with MIs of differing ages and left ventricular locations and 24 patients with no evidence of heart disease were studied. The percent volume of MI was significantly estimated by the initial QRS abnormalities (r = 0.94, p less than 0.00001). The 2 regression equations from the previous training set and from this present test set were compared to verify validity of the criterion, the integral of magnitudes of spatial vectors during initial abnormal depolarization to estimate MI size. There was not a significant difference between the 2 intercepts, the 2 slopes, the 2 straight-line regressions or the 2 correlation coefficients. The additional information obtained from late QRS abnormalities contributed little to improve estimation of size of multiple MIs of differing ages and left ventricular locations, but accurately predicted (r = 0.87) the size in single inferobasal MI. The results indicate that vectorcardiographic measurements of early activation abnormalities is a valid criterion to estimate MI size.

Estimation of inferobasal myocardial infarct size by late activation abnormalities of the QRS complex.

This report describes the relation of myocardial infarct (MI) size in the left ventricular inferobasal wall, measured at necropsy, to late activation abnormalities of the QRS complex, measured by computerized spatial vectorcardiography. Fifteen patients with single inferobasal MIs and 10 patients with no evidence of heart disease were studied. The percentage of MI in the inferobasal wall was significantly related to the vectorcardiographic abnormalities noted late (i.e., 31 +/- 13 ms before the end of the QRS waveform) (r = 0.96, p less than 0.00001). The integral of the vector magnitudes during late abnormal activation significantly predicted the amount of MI in the basal inferior wall (r = 0.88) and in the basal inferior wall plus the outer, subepicardial half of the transmural middle inferior, lateral and inferoseptal walls (r = 0.91). The additional information obtained from late activation of the QRS complex contributed more significance to the estimation of the left ventricular inferobasal MI size than the abnormalities commonly noted during early activation (i.e., during the Q wave).

Infective endocarditis associated with cell wall-deficient bacteria. Electron microscopic findings in four cases.

Although cell wall-deficient bacteria have been isolated in vitro from cases of endocarditis, no pathogenic role has been established for these forms in human disease. One criterion difficult to satisfy is the demonstration of these variants in human tissue, and electron microscopic documentation has not been reported. Cardiac valvular vegetations from four cases of endocarditis were examined by electron microscopy because of unusual histologic features of minimal inflammation and organization and small organisms that stained poorly by Gram stain. Although cell wall-complete bacteria were identified in the specimens, each showed the presence of cell wall-deficient forms within the vegetations; these variants predominated in three cases. Since manifestations of infective endocarditis were present in three cases and conventional cultures were negative, the evidence indirectly suggests a pathogenic role for these aberrant bacteria in human disease.

Fatal parvovirus myocarditis in a 5-year-old girl.

Infection with parvovirus B19 is common in children and typically causes mild illness. We report here the case of a 5-year-old girl who died suddenly, 2 weeks after the clinical diagnosis of a parvoviral infection (erythema infectiosum). Microscopic examination of the heart showed severe myocarditis with extensive T-cell and macrophage infiltration. Cultures, serology, and molecular analyses of serum for enteroviridae, adenovirus, influenza, varicella zoster, cytomegalovirus, and herpes simplex viruses were negative. Quantitative polymerase chain reaction (PCR) analysis for parvovirus B19 in peripheral blood, however, showed active infection (91,000 genomes/mL serum; 2.4 genomes/mononuclear cell). Despite the presence of myocarditis, immunostaining for parvoviral surface antigens was negative in the heart. Quantitative PCR analysis of paraffin sections showed that myocardial parvoviral content was significantly less than that of the normal appearing kidney and within the range predicted simply by tissue blood content. Thus, parvovirus B19 infection can be complicated by fatal myocarditis. Because the virus does not appear to have infected the heart, per se, we speculate that myocarditis arose from immunological cross-reaction to epitopes shared between the virus and the myocardium. HUM PATHOL 32:342-345.

Effect of cyclosporine on the uptake of monoclonal antibody to cardiac myosin.

Monoclonal antibody to cardiac myosin labeled with indium-111 diethylenetriamine pentaacetic acid holds promise as a noninvasive marker of cardiac graft rejection. Uptake of antibody has correlated with histologic evidence of rejection in nonimmunosuppressed animals. Whether this correlation will apply with immunosuppression has important clinical implications. Fifty-two heterotopic heart transplantations were performed between isogeneic and nonisogeneic strains of rats. Cyclosporine-treated (15 mg/kg day subcutaneously for 9 days) and untreated control animals were killed on day 9, 48 hours after injection of radiolabeled antibody. Donor and recipient hearts were submitted for scintillation scanning and histologic analysis. In untreated animals, antibody uptake was significantly greater in nonisogeneic than in isogeneic donor hearts, correlating with a significantly higher rejection score and increased myocyte necrosis in the former. Between isogeneic groups, cyclosporine-treated donor hearts had significantly higher antibody uptake and donor/native antibody uptake ratios than did untreated isogeneic hearts. There was, however, no significant difference in the histologic degree of rejection or myocyte necrosis between isogeneic groups. Between cyclosporine-treated and untreated nonisogeneic animals, donor heart antibody uptake and donor-native heart antibody uptake ratios were not significantly different. Nonetheless, the histologic grade of rejection and presence of myocyte necrosis was significantly greater in untreated than in treated nonisogeneic hearts. There were no abnormalities in the native hearts. In this model, cyclosporine treatment correlates with an increased uptake of antimyosin antibody in both isogeneic and nonisogeneic donor hearts, out of proportion to histologic evidence of rejection or myocyte necrosis. This effect may lead to false-positive results in clinical tests utilizing antimyosin antibody uptake as a marker of rejection in the presence of cyclosporine therapy.

University of Wisconsin solution provides superior myocardial preservation compared with Stanford cardioplegic solution.

The efficacy of the University of Wisconsin solution to safely prolong preservation times for kidney, pancreas, and liver transplantation is established, but its efficacy in enhancing myocardial preservation is not yet clear. We studied the effects of Stanford cardioplegic solution and the University of Wisconsin solution both in preserving the myocardium and in protecting it from the effects of reperfusion injury after 6 hours of preservation. In 28 rat hearts we measured changes in high-energy phosphate content (with magnetic resonance spectroscopy) and histologic changes (edema, endothelial changes, myocyte architecture) during preservation and changes in high-energy phosphate content, histologic status, and performance (aortic systolic and diastolic pressure, heart rate, rhythm) in Langendorff and working hearts during reperfusion. No significant differences in the kinetics of high-energy phosphate changes were noted between the two cardioplegic solutions during preservation. However, at the end of 6 hours of preservation, hearts in the Stanford cardioplegic solution group were more edematous (p < 0.01) than those in the University of Wisconsin group. During reperfusion, no significant differences in the kinetics of high-energy phosphates were noted between the two cardioplegic solutions. None of the hearts in the University of Wisconsin solution group developed ventricular fibrillation at the start of reperfusion, but all hearts in the Stanford group did so. Once sinus rhythm was established no significant differences in developed pressure or heart rate were found between the two solutions. After 2.5 hours of reperfusion, hearts in the Stanford group were more edematous (p < 0.002) and had a greater disruption of myocyte architecture (p < 0.002) and greater arteriolar endothelial injury (p < 0.004). In conclusion, the University of Wisconsin solution better protects the myocardium in this rat model than does Stanford solution. The mechanism for this beneficial effect of the University of Wisconsin solution appears to be due to its better preservation of the microvasculature rather than differences in preservation of high-energy phosphates.

Detection and characterization of atherosclerotic fibrous caps with T2-weighted MR.

PURPOSE: We assessed the performance of T2-weighted MR imaging in detecting atherosclerotic fibrous caps and in depicting their integrity. METHODS: Twenty atherosclerotic lesions removed by carotid endarterectomy were imaged on a 1.5-T system using T2-weighted spin-echo sequences. The MR images were reviewed independently by four blinded interpreters for fibrous caps and ruptures. The results obtained from the observers were then graded against histologic findings by using receiver-operating characteristic (ROC) curve analysis. RESULTS: The area under the ROC curve for fibrous cap detection was 0.80, indicating that T2-weighted MR imaging was a good but not definitively diagnostic test for detecting ex vivo fibrous caps. The ROC curve for fibrous cap characterization yielded an area of 0.75, indicating that T2-weighted MR imaging was a fair but not highly diagnostic test for depicting fibrous cap integrity. A definite reading for detection of fibrous caps or rupture was fairly specific (90% and 98%, respectively) but not very sensitive (37% and 12%, respectively). CONCLUSIONS: T2-weighted MR imaging of ex vivo atherosclerotic plaques aided in the detection and evaluation of fibrous caps. In both cases, MR imaging proved more useful for ruling out disease than for confirming its presence.

Selective myocardial cell necrosis in nonhuman primates.

A retrospective study was performed to describe the histologic stages of selective myocardial cell necrosis (SMCN) in nonhuman primates, and to compare the incidence of SMCN in two groups of nonhuman primates. Myocardial tissues taken at the time of autopsy from 50 primates at an experimental center were compared with similar tissues from 50 primates housed in a breeding colony. SMCN was confirmed in 20% of the experimental primates and 30% of the breeding primates, proportions that were not significantly different. The incidence and histologic characteristics of SMCN in nonhuman primates were similar to those described in humans, and resembled the lesion produced in experimental primates by administration of catecholamines of by hypokalemia.