PubMed Health⌕ Search

Biomedical subjects

Charles C Marboe

Publications and source records attributed to Charles C Marboe.

9 recordsLinked to original sources
PubMed2005

Mechanical unloading leads to echocardiographic, electrocardiographic, neurohormonal, and histologic recovery.

BACKGROUND: Mechanical unloading during left ventricular assist device (LVAD) support may lead to cardiac recovery. Predictors of recovery, however, have not been identified. We aimed to evaluate the time course and durability of echocardiographic, electrocardiographic (ECG), histologic, and neurohormonal changes that occur with LVAD support and to screen for non-invasive markers of cardiac recovery. METHODS: LVAD patients underwent monthly testing, including echocardiographic, ECG, and serum B-type natriuretic peptide (BNP) measurement. Paired myocardial tissue samples from implant and explant were also analyzed. RESULTS: Thirty-six LVAD patients were prospectively followed for an average of 101 +/- 99 days. Left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD) significantly improved at 30 days compared with pre-LVAD (19% +/- 6.6% vs 33% +/- 8.1%, 7.1 +/- 1.2 cm vs 4.9 +/- 1.0 cm, respectively; both p < 0.001), with no improvement thereafter. At 30 days, QRS duration and QTc interval were significantly decreased from pre-LVAD (both p < 0.05). There was a marked reduction in BNP, myocyte size, and collagen deposition with LVAD support (all p < 0.01). In screening for markers of recovery, the decrease in QTc was inversely related to LVEDD at 60 days. Changes in QRS and myocyte diameter also correlated with the improvement in LVEF at 30 days. No patients had sufficient recovery for device explantation. CONCLUSIONS: We demonstrate echocardiographic, ECG, histologic, and neurohormonal improvement during LVAD support. Cardiac recovery peaked by 60 days, and there was a trend toward progressive improvement in QRS duration with ongoing support. We report the association of ECG changes with echocardiographic and histologic improvements. Future prospective studies may yield important markers of recovery.

Adolescent↗
PubMed2005

Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.

In 1990, an international grading system for cardiac allograft biopsies was adopted by the International Society for Heart Transplantation. This system has served the heart transplant community well, facilitating communication between transplant centers, especially with regard to patient management and research. In 2004, under the direction of the International Society for Heart and Lung Transplantation (ISHLT), a multidisciplinary review of the cardiac biopsy grading system was undertaken to address challenges and inconsistencies in its use and to address recent advances in the knowledge of antibody-mediated rejection. This article summarizes the revised consensus classification for cardiac allograft rejection. In brief, the revised (R) categories of cellular rejection are as follows: Grade 0 R--no rejection (no change from 1990); Grade 1 R--mild rejection (1990 Grades 1A, 1B and 2); Grade 2 R--moderate rejection (1990 Grade 3A); and Grade 3 R--severe rejection (1990 Grades 3B and 4). Because the histologic sub-types of Quilty A and Quilty B have never been shown to have clinical significance, the "A" and "B" designations have been eliminated. Recommendations are also made for the histologic recognition and immunohistologic investigation of acute antibody-mediated rejection (AMR) with the expectation that greater standardization of the assessment of this controversial entity will clarify its clinical significance. Technical considerations in biopsy processing are also addressed. This consensus revision of the Working Formulation was approved by the ISHLT Board of Directors in December 2004.

Biopsy↗
PubMed2005

Successful bilateral lung transplantation for pulmonary fibrosis associated with the Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism, a bleeding diathesis, and in a subset of patients, pulmonary fibrosis. Lung transplantation, the only curative therapy for pulmonary fibrosis, has not been previously reported as a successful treatment strategy for patients with HPS because the bleeding diathesis was thought to contraindicate major thoracic surgery. We successfully performed bilateral sequential lung transplantation in a patient with pulmonary fibrosis and HPS after transfusion of 6 units of platelets. Lung transplantation is a viable therapeutic option in patients with pulmonary fibrosis and only a mild bleeding diathesis associated with HPS.

Adult↗
PubMed2005

Nodular endocardial infiltrates (Quilty lesions) cause significant variability in diagnosis of ISHLT Grade 2 and 3A rejection in cardiac allograft recipients.

BACKGROUND: Endomyocardial biopsy is used to guide therapy after heart transplantation. An accurate and reliable diagnosis of rejection is critical for proper patient management. METHODS: A sub-set of 827 biopsies from 273 patients were identified from 8 centers participating in the Cardiac Allograft Gene Expression Observational Study. These included all biopsies graded by local center pathologists as International Society for Heart and Lung Transplantation (ISHLT) Grade 1B or higher and also randomly chosen Grade 0 and 1A biopsies. Each of these cases was reviewed in a blinded manner by 3 study pathologists in the absence of clinical data. The study pathologists were assigned an ISHLT grade and noted nodular endocardial infiltrates (Quilty lesions). RESULTS: The study pathologists were significantly more likely than local pathologists to diagnose ISHLT Grade 0, 1A and 3B rejection and significantly less likely to diagnose ISHLT Grade 1B, 2 and 3A rejection. Concordance between local and study pathologists was lowest for Grade 2 (17% agreement). Quilty lesions were noted in 3.3% of local Grade 0 cases and in 31% and 37% of local Grade 2 and 3A cases, respectively. Quilty lesions were recognized by study pathologists in 35% of local Grade 2 cases "downgraded" to Grade 0 or 1, but in only 10% of local Grade 2 cases confirmed by study pathologists. CONCLUSIONS: The greatest variability between pathologists in application of the ISHLT grading system is in Grade 2 biopsies, and Quilty lesions are a major contributing factor to the lack of concordance. Accurate application of the ISHLT grading system requires improved recognition and understanding of Quilty lesions.

Adolescent↗
PubMed2002

Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles.

BACKGROUND: The exact role of adrenoceptors in norepinephrine (NE)-mediated regulation of the human coronary circulation has yet to be elucidated. Thus, the goals of this study were to characterize the adrenoceptors involved in the responses to NE in isolated human coronary arterioles and small arteries. METHODS AND RESULTS: Arterioles (n=39) and small arteries from the left ventricle of explanted human hearts were isolated and cannulated. Vessels from the hearts of 21 patients were studied: 15 males and 6 females, aged 0.5 to 63 years. Nineteen patients were considered to be New York Heart Association class 4. All hearts exhibited hypertrophy (190+/-20%). The passive diameter of arterioles was 167+/-8 microm (range 97 to 323 microm). NE (10(-7) to 3x10(- 7) mol/L) elicited concentration-dependent dilations (47+/-4 microm) that were unaffected by endothelium removal, N(omega)-nitro-L-arginine (10(- 4) mol/L, an NO synthase inhibitor), or practolol (10(-6) mol/L, a beta1-receptor blocker). However, administration of propranolol (10(-5) mol/L, a combined beta1- and beta2-blocker) or butoxamine (10(-6) mol/L, a beta2-receptor blocker) completely eliminated the NE-induced dilation. Constrictions to NE (2 of 39 vessels) were inhibited by prazosin (10(-6) mol/L, an alpha1-receptor blocker). Methoxamine (10(-9) to 10(-5) mol/L, an alpha1-agonist) had no effect, whereas U44619, a thromboxane mimetic, elicited dose-dependent constriction of vessels. CONCLUSIONS: Our data indicate that isolated human coronary arterioles and small arteries dilate to NE via beta2-receptors on smooth muscle. These findings are important to our understanding of the mechanisms action of NE in the human coronary circulation.

Adolescent↗
PubMed2002

Cellular electrophysiologic properties of old canine atria provide a substrate for arrhythmogenesis.

OBJECTIVE: The incidence of atrial fibrillation increases with age. We hypothesized that aging-associated changes in the atrial action potential (AP) and conduction velocity provide a substrate for abnormal conduction and arrhythmogenesis. METHODS: We used microelectrode techniques to record AP from the endocardium of the right atrial wall of dogs aged 1-5 (adult) and >8 years (old). Conduction velocity was measured between two microelectrodes 3-10 mm apart. Histological study was carried out to assess fibrosis. RESULTS: Whereas resting potential, AP amplitude and V(max) did not differ with age, the plateau was more negative and AP duration was longer in old tissue. The L-type calcium current (I(Ca,L)) agonist Bay K8644 (10(-8)-10(-6) mol/l) elevated the plateau and shortened APD more in old than in adult, such that AP contour in old atria approached that of adult. In contrast, the I(Ca,L) blocker nisoldipine (10(-8)-10(-5) mol/l) depressed the plateau in adult and had no effect in old. There was no difference between the two groups in conduction velocity of normal beats, whereas for early premature impulses, reduced conduction velocity and a wider time window manifesting slow conduction were detected in old in comparison to adult tissue. A twofold increase in the amount of fibrous tissue was detected in old atria. CONCLUSIONS: Our data show significant differences in contour of AP in adult and old atria. The responses to Bay K8644 and nisoldipine suggest a decreased I(Ca,L) in old atrial tissue. The alterations in AP contour and increased fibrosis may be responsible for slower conduction of early premature beats in old atria. The age-related changes in conduction of premature beats are consistent with those observed in patients with paroxysmal atrial fibrillation and may contribute to the greater propensity to atrial fibrillation in the aged.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMedDate not supplied

The relationship of nodular endocardial infiltrates (Quilty lesions) to survival, patient age, anti-HLA antibodies, and coronary artery disease following heart transplantation.

BACKGROUND: Quilty lesions are mononuclear cell infiltrates identified in human heart transplant biopsies. The biologic significance of Quilty lesions remains undetermined. METHODS: We monitored acute rejection by biopsy and lymphocyte growth assay (LGA) as well as transplant-related coronary artery disease (TRCAD) by yearly angiogram in 285 recipients of primary heart allografts. Patients showing Quilty lesions on biopsies during the first year posttransplant were compared with patients without such lesions. Recipients' sera were obtained at the time of biopsy and tested for anti-HLA Class I and II antibodies. RESULTS: The actuarial survival of patients who developed Quilty lesions was significantly better than those who did not (P=.0074). Patients with Quilty lesions were younger and more likely to have a biopsy diagnosis of acute rejection (P=.002) and positive LGA (P<.0001) during the first posttransplant year. Among patients who do not form anti-HLA Class II antibodies, those with Quilty lesions were more likely than patients without Quilty lesions to develop TRCAD 5 years posttransplantation (P=.04). There was no correlation of Quilty status with the number of HLA donor-recipient mismatches or posttransplant development of anti-HLA antibodies. CONCLUSIONS: Quilty formers showed improved survival and are more likely to be diagnosed with acute rejection on biopsy and have positive LGAs. Allograft recipients who do not form anti-HLA Class II antibodies but do form Quilty lesions are more likely to develop TRCAD by 5 years posttransplantation than those who do not form Quilty lesions.

Adolescent↗