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Biomedical subjects

J Narula

Publications and source records attributed to J Narula.

At least 109 records · Page 6Linked to original sources
PubMed1988

Spatial quantitative vectorcardiography in aortic stenosis: correlation with hemodynamic findings.

Thirty-four patients with hemodynamically documented valvar aortic stenosis without congestive heart failure were studied by the corrected Frank lead system vectorcardiography, with special emphasis on the angular characteristics of spatial R max to define the severity of the lesion. Spatial QRS-T angle demonstrated a highly significant correlation with the peak left ventricular systolic pressure (r = 0.72, P less than 0.001) and a significant correlation with peak transvalvar aortic gradient (r = 0.49, P less than 0.01). Furthermore, all patients with a QRS-T angle of more than 90 degrees had significant aortic stenosis (TVG greater than or equal to 50 mm Hg). The peak left ventricular systolic pressure and transvalvar aortic gradient also demonstrated a significant negative correlation with azimuth angle (r = -0.36 and -0.34, respectively; P less than 0.05) and a positive correlation with spatial R max magnitude (r = 0.38 and 0.41, respectively; P less than 0.05). There was no correlation between elevation angle of spatial R max and left ventricle systolic pressure or transvalvar aortic gradient. Our study indicates that spatial quantitative vectorcardiographic angular characteristics, particularly spatial QRS-T angle, may be a useful adjunct to other noninvasive techniques to assess the severity of valvar aortic stenosis.

Adolescent↗
PubMed1988

Immunohistochemical characterisation of Aschoff nodules and endomyocardial inflammatory infiltrates in left atrial appendages from patients with chronic rheumatic heart disease.

Fifty left atrial appendages collected fresh during closed mitral valvotomy in patients with chronic rheumatic heart disease, were analysed to determine the frequency of Aschoff nodules and characteristics of mononuclear inflammatory infiltration. Fifty-six percent of specimens demonstrated Aschoff nodules with no clinical or laboratory evidence of acute rheumatic activity in the patients undergoing surgery. Endomyocardial infiltration contained predominantly T cells and occasionally B cells. The relative proportions of T helper-inducer, T suppressor-cytotoxic lymphocytes and macrophages were 45.1 +/- 7.6, 23.5 +/- 4.8 and 29.3 +/- 9.6%, respectively. Frequent presence of Aschoff nodules and heavy mononuclear infiltrates in chronic rheumatic heart disease suggests a possibility of subclinical ongoing carditis.

Adolescent↗
PubMed1988

Evaluation of patients with bundle branch block and "unexplained" syncope: a study based on comprehensive electrophysiologic testing and ajmaline stress.

Thirty-five patients with bundle branch block (BBB) and unexplained syncope underwent electrophysiologic study (EPS) including programmed ventricular stimulation and ajmaline administration (1 mg/kg, IV) to induce infra-His block. A prolonged HV interval (greater than 55 ms) was present in 16 of the 35 patients. Ajmaline-induced HV block occurred in 12 patients (complete HV block in 10, and 2:1 HV block in two). Monomorphic ventricular tachycardia (VT) was inducible in nine (25.7%) and polymorphic VT in two patients (5.7%). Left ventricular ejection fraction (LVEF) was less than 40% in five patients (45.5%) with inducible VT. Two patients had an unexpected co-existence of inducible HV block and VT. The remaining 14 patients (40%) had no detectable abnormality. The incidence of inducible VT was higher (45% vs 13.3%), and the presence of negative studies was lower (30% vs 53.3%) in patients with structural heart disease (n = 20), when compared to those with no significant heart disease (n = 15) (differences not significant [NS]). During a mean follow-up period of 16.5 +/- 9.2 months, all the patients with inducible HV block have been asymptomatic after having received permanent pacemakers. Patients with inducible monomorphic VT (except one with poor left ventricular function who died suddenly) have also been asymptomatic on antiarrhythmic drugs. Of the remaining patients, seven with normal EPS, two with prolonged HV intervals but no inducible HV block (despite being given permanent pacemakers) and one patient with polymorphic VT on antiarrhythmic drugs continue to have recurrent syncope. Approximately 60% of patients with BBB and unexplained syncope have clinically significant electrophysiologic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Coronary arteritis in nonspecific aortoarteritis.

Nonostial distal coronary artery involvement in nonspecific aortoarteritis is rare. We report a 35-year-old patient with features of nonspecific aortoarteritis who had an inferolateral myocardial infarction and on coronary angiography was shown to have severe disease of the left circumflex artery in its middle third.

Adult↗
PubMed1985

Ajmaline-induced torsade de pointes.

A patient with primary myocardial disease and left bundle-branch block who developed marked QT prolongation and torsade de pointes following an intravenous injection of ajmaline during an electrophysiologic study is reported. The patient could be resuscitated successfully 1 h after the onset of tachycardia.

Ajmaline↗
PubMedDate not supplied

Pulmonary varix associated with mitral valve disease.

A case of pulmonary varices with mitral valve disease is presented with a detailed review of the literature. Two distinct categories of the disease, with and without left atrial hypertension, are emphasized.

Adolescent↗
PubMedDate not supplied

Immunologic and immunogenetic studies in rheumatic fever and rheumatic heart disease.

In order to evaluate all the important limbs of the immune system in the same patient population with rheumatic fever (RF) and rheumatic heart disease (RHD) cellular and humoral immune parameters as well as the immunogenetic profile in 265 North Indian patients with RHD were evaluated. They were studied for class in HLA antigens and 165 of them were also evaluated for the class II (DR locus) antigen profile. Data obtained was compared with 400 and 134 healthy controls respectively of the same ethnicity. Humoral immune parameters (Serum immunoglobulins IgG, IgA; Serum complement fractions C3, C4, C3d; circulating immune complexes and B lymphocyte numbers) and cellular immune parameters (total leucocyte and lymphocyte counts; T lymphocyte sub-populations--CD4, CD8 counts; lymphocyte migration inhibition to an extracellular streptococcal antigen, streptolysin 'O') were studied in 23 patients with RF, 21 patients with "inactive" RHD and 20 normal controls. Patients of RHD were noted to have an increased frequency of DR3 (P less than 0.001; Relative risk = 2.3) and a decreased frequency of DR2 (P less than 0.001; Relative risk = 0.3) as compared to the controls. Patients of RF had evidence of an altered regulatory T cell function (increased CD4/CD8 ratio) and decreased cell mediated immunity to streptolysin 'O'. An increased humoral immune response (increased B cell counts, elevated serum IgG, circulating immune complexes and C3d) was noted in patients of RF as well as "inactive" RHD. An integrated pathogenetic model with immune response associated antigens of the DR locus influencing selection of cardiac cross-reactive antigens by the antigen processing macrophages, an altered regulatory T cell function with decreased suppressor T cell activity leading to an abnormal immune response is proposed to explain the pathogenesis of RF.

HLA Antigens↗
PubMedDate not supplied

Antibody imaging in the evaluation of cardiovascular diseases.

Antimyosin antibody was originally developed for in vivo detection of acute myocardial infarction. However, its utility has expanded to include diagnosis of various cardiovascular diseases in which myocyte necrosis constitutes an obligatory component of the disease. Thus antimyosin has also been used clinically for noninvasive diagnosis of acute myocarditis, heart transplant rejection, drug-induced cardiotoxicity, and other cardiomyopathies. This first-generation monoclonal antibody, antimyosin, has opened the way for the second-generation monoclonal antibodies such as antifibrin and antiplatelet for in vivo diagnostic use in the detection of deep venous thrombosis and pulmonary embolism and antiatherosclerotic lesion-specific antibody for diagnosis of metabolically active lesions. Whether the third generation of antibodies will include ultrasmall antigen-binding units or negative charge-modified antibodies must await future studies.

Animals↗
PubMedDate not supplied

Burden of myocardial damage in cardiac allograft rejection: scintigraphic evidence of myocardial injury and histologic evidence of myocyte necrosis and apoptosis.

BACKGROUND: Because myocardial damage determines morbidity and outcomes in heart transplant rejection, assessment of total burden of myocardial damage is highly desirable. In addition to myocyte necrosis, programmed cell death, or apoptosis, has recently been shown to contribute to cardiac allograft rejection. In the present study, we noninvasively determined myocardial damage by antimyosin scintigraphy and compared it with necrotic and apoptotic myocardial damage in endomyocardial biopsy (EMB) specimens. METHODS AND RESULTS: Forty scintigraphic and histologic studies were simultaneously performed. Of these, 19 patients had no EMB evidence of allograft rejection (group I, International Society of Heart and Lung Transplantation [ISHLT] grade 0/4), 12 had mild rejection (group II, ISHLT grades 1A and 1B), and 9 had evidence of moderate allograft rejection (group III, ISHLT grades 2, 3A, and 3B). None of the biopsies demonstrated severe allograft rejection (ISHLT grade 4/4). The severity of global myocyte damage in 40 patients was assessed by antimyosin scintigraphy. Endomyocardial biopsies were performed in these patients within 48 hours of imaging study; biopsy specimens were characterized for presence of myocyte necrosis and apoptosis. Evidence of myocyte necrosis was observed in 9 (23%) of 40 EMB specimens. Nineteen EMB specimens of group I had no inflammation and no myocyte necrosis, 12 of group II specimens showed interstitial mononuclear cell infiltration (only) but no myocyte necrosis, and all 9 of group III specimens had evidence of cellular infiltration and myocyte damage. Myocyte necrosis was assessed by hematoxylin-eosin and trichrome staining of EMB specimens. On the other hand, apoptosis of myocytes, as assessed by TUNEL staining of DNA fragments, was seen in 22 (55%) of the 40 biopsy specimens: 47%, 58%, and 67% in groups I, II and III, respectively. Abnormal antimyosin scan findings, indicating presence of myocardial damage, were observed in 9 of the 19 patients in group I and in all patients in groups II and III. Although positive antimyosin scan results in group III patients are concordant with the presence of histologic myocardial necrosis, myocardial uptake of antimyosin antibodies in groups I and II (no apparent myocyte damage at light microscopic examination) could reflect either sampling error of the biopsy or ongoing apoptotic myocyte damage. CONCLUSIONS: Apoptosis of myocytes is frequently observed during cardiac allograft rejection. The presence of apoptotic myocytes in the absence of histologic rejection activity in patients with antimyosin uptake suggests that apoptosis could be an additional mechanism of transplant-associated myocardial damage.

Adult↗
PubMedDate not supplied

In vivo targeting of acute myocardial infarction with negative-charge, polymer-modified antimyosin antibody: use of different cross-linkers.

BACKGROUND: Cell surfaces and intercellular matrixes contain acidic residues, making them negatively charged. Antibodies are basic, positively charged glycoproteins. Therefore the potential for nonspecific ionic interaction exists, which could increase the background activity. Modification of antibodies with negatively charge-modified polymers have been shown to reduce this nonspecific background activity. This study was performed to investigate the appropriateness of different cross-linkers used covalently to link the chelating negatively charge-modified polylysine to antimyosin Fab (AM-Fab). The cross-linking was performed through peptide (AM-I) or thioether (AM-II) bonds. The in vitro evaluation of the immunointegrity and the in vivo assessment were performed to investigate the potential for reduction of nontarget background activity. Furthermore, the role of the charge of the polymers (whether completely negatively charge modified by succinylation [AM-IIs] or only partially negatively charge modified [AM-IIns]) was also assessed. METHODS AND RESULTS: All polymer-modified preparations (AM-I, AM-IIs, and AM-IIns) retained the immunoreactivities relative to the unmodified or conventional diethylenetriaminepentaacetic acid-coupled AM-Fab as assessed by radioimmunoassay or enzyme-linked immunosorbent assay. These polymer-modified preparations labeled with 111In were assessed in 13 rabbits with acute experimental myocardial infarction. Acute infarcts were produced by 40 minutes of left anterior descending coronary artery occlusion followed by reperfusion. At between 10 and 30 minutes of reperfusion, 10.4 +/- 1.8 mBq 111In-AM-I (10 to 20 micrograms; n = 7) or 11.4 +/- 2.3 mBq 111In-AM-II (n or ns) (20 to 25 micrograms; n = 6) was administered intravenously. Gamma imaging was performed in the left lateral position and arterial blood samples were withdrawn serially for the next 3 hours. At the end of the final imaging session, AM-I uptake was determined to be 1.09% +/- 0.11% (mean percent injected dose per gram myocardium +/- SEM) in 20 infarcted myocardial segments from seven rabbits, compared with 0.031% +/- 0.003% in 20 normal myocardial segments (infarct/normal myocardial ratio 53.9 +/- 18.41). The mean percent injected dose of 111In-labeled thioether-linked AM-Fab preparations in nine infarcted myocardial segments from each group was 0.067% +/- 0.008% (infarct/normal myocardial ratio 9.0 +/- 1.5) and 0.144% +/- 0.011% (infarct/normal myocardial ratio 10.2 +/- 1.9) with AM-IIs (n = 3) and AM-IIns (n = 3), respectively (p < 0.0001). The non-target organ distribution of the AM-I and AM-IIs was similar. AM-IIns preparation resulted in high non-target organ activities. CONCLUSIONS: This study shows that the charge of the antibody can be manipulated favorably by cross-linking with negatively charged polymers, which results in the reduced in vivo non-target organ activities. Charge modification does not adversely affect the apparent affinity of the antibody. However, the type of cross-linkers used may significantly influence the in vivo stability of the modified antibody preparations for target organ visualization. These data may find potential application in future clinical imaging protocols.

Animals↗
PubMedDate not supplied

Antimyosin uptake and myofibrillarlysis in dilated cardiomyopathy.

BACKGROUND: Although antimyosin scintigraphy detects myocyte necrosis associated with myocarditis, it has also been reported to yield positive results in a large number of patients with clinical dilated cardiomyopathy without histologic evidence of myocarditis. The question to be resolved is whether this discordance represents false-positive results of antimyosin scans or whether antimyosin scintigraphy more accurately identifies the presence of myocyte necrosis than does endomyocardial biopsy testing. METHODS AND RESULTS: Forty patients with the acute onset of dilated cardiomyopathy (left ventricular ejection fraction < 45%; mean 27% +/- 11%) but no endomyocardial biopsy evidence of myocarditis, were identified from a consecutive series of 50 patients who had undergone indium 111 antimyosin antibody scintigraphy and endomyocardial biopsy for suspected myocarditis. The endomyocardial biopsy specimens were analyzed to identify features correlating with antimyosin uptake or improvement in left ventricular ejection fraction (LVEF) over time. Twenty-five patients showed left ventricular myocardial uptake of radiolabeled antimyosin antibody by both planar and tomographic imaging. The remaining 15 patients had no antimyosin uptake. Of the 25, 22 (88%) patients with positive findings on antimyosin scans had degenerated, myofibrillarlytic myocytes in their biopsy specimens. Of the 15 patients with negative findings on antimyosin scans, only 6 (40%) had similar myofibrillarlytic myocytes (chi 2 = 8.13; p < 0.0047). No other histological feature correlated with the antimyosin positivity. Stepwise multiple regression analysis was performed for identification of predictors of short-term improvement in LVEF. Patients with positive findings on antimyosin scans showed a trend toward improvement with time (F = 3.97; p > 0.05). None of the histologic features predicted improvement in the LVEF. However, the combination of positive findings on an antimyosin scan and myofibrillarlysis did correlate significantly with spontaneous improvement in ejection fraction (F = 4.53; 0.01; < p < 0.05). CONCLUSIONS: This study identifies myofibrillarlysis as a common pathologic alteration in patients with recent onset of dilated cardiomyopathy and positive findings on antimyosin scan, who lack right ventricular biopsy evidence of myocarditis. Because myofibrillarlytic cell population may represent a histologic spectrum of viable to necrotic myocytes, it appears that antimyosin uptake detects necrotic myofibrillarlytic myocytes that are not identified by light microscopy.

Adolescent↗
PubMedDate not supplied

Gamma imaging of atherosclerotic lesions: the role of antibody affinity in in vivo target localization.

BACKGROUND: Monoclonal antibodies are attractive agents for noninvasive localization of various cardiovascular disorders. Because proliferating intimal smooth muscle cells are important components of atherosclerotic lesions, radiolabeled antibody Z2D3 specific for proliferating smooth muscle cells has been used for immunoscintigraphic localization of experimental atherosclerotic lesions. This study was undertaken to assess the role of antibody affinity in optimization of immunoscintigraphic localization of these lesions. Z2D3 belongs to the immunoglobulin (Ig) M class of antibodies. For immunoscintigraphic studies, attempts were made to prepare F(ab')2 or Fab fragments from the parent cell line. Fragmentation of Z2D3-IgM or its two subclones (B7 and 2B12) was not possible; therefore the parent hybridoma line was subjected to class switching. Cell lines 5C5 and 3E5 secreted antibody of the IgG1 subclass. The Z2D3-IgG1 antibodies were enzymatically digested to provide F(ab')2. Because of a tenfold loss of immunoreactivity of these class-switched antibodies, the parent clone was subsequently genetically engineered to obtain a mouse/human chimeric antibody with human IgG1 constant region. F(ab')2 of Z2D3-73.30 chimeric antibody retained the immunoreactivity relative to the original Z2D3-IgM. Radiolabeled murine and chimeric F(ab')2 fragments were used to assess the role of affinity in gamma scintigraphic visualization of experimental atherosclerotic lesions. METHODS AND RESULTS: Experimental atherosclerotic lesions were induced in 19 rabbits by abdominal aortic balloon deendothelialization followed by a hyperlipidemic diet for 12 weeks. 111In-labeled chimeric high-affinity Z2D3 F(ab')2 fragments (111In-Hi.aff Z2D3) were administered in four animals. Uptake was compared with 111In-labeled F(ab')2 of nonspecific human IgG1 (n = 4), murine low-affinity Z2D3-5C5 (111In-Lo.aff Z2D3; n = 4), nonspecific murine IgG1 monoclonal antibodies (n = 4), and 123I-labeled murine low-affinity Z2D3-3E5 (n = 3). Atherosclerotic lesions were visualized 48 hours after administration of the chimeric Hi.aff-Z2D3 antibody in all animals. Lesions were not visualized in rabbits injected with Lo.aff-Z2D3 or murine or human nonspecific antibodies. Mean percent injected dose per gram in the lesion was significantly higher with the 111In-Hi.aff-Z2D3 (0.112% +/- 0.024%) compared with 111In-Lo.aff-Z2D3 (0.037% +/- 0.005%; p = 0.03), human nonspecific (0.027% +/- 0.004%; p = 0.01), or murine nonspecific antibodies (0.006% +/- 0.001%; p = 0.0004). Nonspecific activity in unballooned thoracic aortic segments (normal) was comparable in the 111In-Hi.aff-Z2D3 (0.019 +/- 0.003) and the 111In-Lo.aff-Z2D3 (0.011% +/- 0.005%; p = 0.3) antibodies. The lesion activities of the Lo.aff-Z2D3 labeled with 111In (0.037 +/- 0.005) or 123I (0.034 +/- 0.007; p = 0.71) were similar regardless of the radioisotopes used for labeling. CONCLUSIONS: Our study demonstrates that the specificity of an antibody for the target antigen in the atheroma is a necessary condition for in vivo targeting. However, high enough affinity of an antibody is an essential component for noninvasive diagnostic visualization of experimental atherosclerotic lesions.

Animals↗
PubMedDate not supplied

Diagnostic accuracy of antimyosin scintigraphy in suspected myocarditis.

BACKGROUND: Radiolabeled antibody specific for cardiac myosin administered intravenously has been used to define noninvasively regions of myocardial necrosis. Inflammatory heart disorders such as myocarditis and heart transplant rejection demonstrate diffuse and often faint myocardial uptake of antimyosin antibody. This study was undertaken to evaluate the reproducibility and diagnostic accuracy of antimyosin antibody imaging for the detection of patients with suspected myocarditis. METHODS AND RESULTS: Fifty antimyosin scans, performed consecutively in patients with suspected myocarditis, were evaluated by one independent observer and two panels of observers. Antimyosin scan interpretations were compared with endomyocardial biopsy results and also with serial changes in left ventricular function. An independent observer (A) and a panel of five observers (A through E) interpreted the antimyosin scans as positive or negative on the basis of both planar images and tomographic reconstructions. Three of the five observers (A through C) again interpreted the scans but based interpretation only on planar images. Blinded random sequence evaluation of antimyosin scans based on the planar and tomographic interpretations revealed moderate agreement between the independent observer (A) and the group of observers (A through E) (kappa = 0.58). There was also moderate agreement between interpretations based on planar images alone and interpretations based on both planar and tomographic images (kappa [A through E]/[A through C] = 0.57; kappa [A through C]/A = 0.48). Comparison of antimyosin scan results with histologic evidence of myocarditis in endomyocardial biopsy specimens demonstrated that all scan results obtained from the individual or the panels of observers had a very high sensitivity (91% to 100%) and a high negative predictive value (93% to 100%). The specificity (31% to 44%) and positive predictive value (28% to 33%) were less impressive. We also compared the scan and biopsy results with the composite clinical standard of significant left ventricular functional improvement. Endomyocardial biopsy demonstrated poor sensitivity (35%) compared with antimyosin scans (82% to 94%) but had superior specificity (endomyocardial biopsy, 79%; antimyosin scan, 25% to 42%). The specificity of interpretations based on planar and tomographic interpretations (38% to 42%) was better than the planar images alone (25%). If reversible left ventricular dysfunction is considered clinical evidence of myocarditis, this study suggests that a negative endomyocardial biopsy significantly misses the presence of the disease. On the other hand, a negative antimyosin scan almost invariably excludes myocarditis. CONCLUSIONS: This study demonstrates a high degree of interobserver reproducibility of antimyosin interpretation. Comparison of the scintigraphic results with histologic and clinical standards indicates a high sensitivity of antimyosin scans for the detection of myocarditis. The antimyosin scan is also not likely to miss clinically or pathologically diagnosed myocarditis, in contrast to the endomyocardial biopsy, which missed clinically validated myocarditis 65% of time. The combination of high sensitivity and negative predictive value suggests that antimyosin scintigraphy may be an effective screening procedure for obviating biopsies in patients with suspected myocarditis.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Maximizing radiotracer delivery to experimental atherosclerotic lesions with high-dose, negative charge-modified Z2D3 antibody for immunoscintigraphic targeting.

BACKGROUND: Two factors that directly affect target/background ratio in immunoscintigraphy are the concentration of the antibody bound to the target and the concentration of the antibody in the circulation. High dosages of monoclonal antibody have been reported to be more efficacious in visualization of tumors. Although administration of a higher dosage of antibody increases the absolute target accumulation of the radiotracer, it also increases the background activity, which may offset this advantage. Negative charge-modified antibodies carry high specific radioactivity to the target sites without significantly increasing the background activity. Therefore we investigated whether higher dosages of negative charge-modified antibody can be used to improve imaging of experimental atherosclerotic lesions. METHODS AND RESULTS: Experimental atherosclerotic lesions were produced in 16 New Zealand White rabbits by balloon deendothelialization of the infradiaphragmatic aorta and hyperlipidemic diet for 12 weeks. Negative charge-modified Z2D3 antibody F(ab')2 specific for an antigen on proliferating smooth muscle cells of human atheroma labeled with (111)In was used for imaging experimental atherosclerotic lesions either at high (100 to 125 microg) or low (25 to 50 microg) dosages. A lower dosage of Z2D3 was labeled with 507 +/- 29.5 microCi (25 to 50 microg) (111)In label, compared with 2.9 +/- 0.24 mCi (100 to 125 microg) for the higher dosage. Although noninvasive visualization of atherosclerotic lesions was possible in all animals at 24 hours, high antibody dose allowed unequivocal visualization of the lesion as early as 3 hours after intravenous administration of the antibody. Eight animals were killed at 24 hours and the remaining eight animals at 48 hours. Mean radioactivity dose delivered per gram of lesion with the low-dose protocol at 24 hours was 0.46 +/- 0.09 microCi, which remained essentially unchanged at 48 hours (0.37 +/- 0.09 microCi; p = 0.51). With the high-dosage protocol, the total radioactivity (dose) per gram uptake in the lesion increased by about eightfold (3.49 +/- 0.58 microCi; p = 0.002) at 24 hours and was sixfold higher at 48 hours (2.21 +/- 0.45 microCi; p < 0.02). CONCLUSIONS: The study demonstrated that the increase in the dosage of negatively charge-modified antibody allows a very high delivery of specific radioactivity to the target, which in turn enables early visualization of experimental atherosclerotic lesions.

Animals↗
PubMedDate not supplied

Avidity of technetium 99m glucarate for the necrotic myocardium: in vivo and in vitro assessment.

BACKGROUND: Similar to other 99mTc-based infarct-avid agents, 99mTc-glucarate localizes in myocardial infarcts. Whether severely ischemic viable myocytes sequester 99mTc-glucarate is uncertain. To assess the infarct specificity, in vitro and in vivo studies were performed. METHODS AND RESULTS: H9C2 embryonic rat cardiocytes cultured under normoxia (N) or hypoxia (H) for 24 hours in 7.5 muCi 99mTc-glucarate were compared with necrotic cardiocytes. Mean H/N ratio (3.0 +/- 0.004, mean +/- SD) was significantly less than that of the necrotic/N ratio (39.9 +/- 6.5, p < 0.01). Reperfused myocardial infarction (MI) in 4 dogs confirmed by 201Tl (0.5 to 1.0 mCi) scintigraphy were imaged serially with simultaneously injected mixture of 99mTc-glucarate and 111In-antimyosin Fab. Infarcts were detected scintigraphically within 4 to 10 minutes with 99mTc-glucarate. 111In-antimyosin required more than 1 hour. Myocardial distribution at 5 hours showed a direct correlation between 99mTc-glucarate and 111In-antimyosin uptake (r = 0.99, p < 0.0001). Both 99mTc-glucarate (r = -0.777, p < 0.0001) and 111In-antimyosin (r = -0.775, p < 0.0001) were inversely related to 201Tl distribution. CONCLUSIONS: The near perfect correlation between 99mTc-glucarate and 111In-antimyosin uptake (r = 0.99) in reperfused canine MI and the insignificant glucarate uptake by viable cardiocytes in vitro attest to the avidity of 99mTc-glucarate for the necrotic myocardium and favor its use as a specific early marker of myocyte necrosis in acute MI.

Animals↗