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Title: Regional pulmonary perfusion following human heart-lung transplantation

Abstract

Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

Authors:
; ; ; ; ;  [1]
  1. (Royal Victoria Hospital, Montreal, Quebec (Canada))
Publication Date:
OSTI Identifier:
5672279
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Nuclear Medicine; (USA); Journal Volume: 30:8
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; HEART; BLOOD FLOW; LUNGS; ISOMERIC NUCLEI; MAN; PERFUSED ORGANS; SCINTISCANNING; SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY; TECHNETIUM 99; TRANSPLANTS; XENON ISOTOPES; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BODY; CARDIOVASCULAR SYSTEM; COMPUTERIZED TOMOGRAPHY; COUNTING TECHNIQUES; DIAGNOSTIC TECHNIQUES; EMISSION COMPUTED TOMOGRAPHY; HOURS LIVING RADIOISOTOPES; INTERMEDIATE MASS NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; MAMMALS; NUCLEI; ODD-EVEN NUCLEI; ORGANS; PRIMATES; RADIOISOTOPE SCANNING; RADIOISOTOPES; RESPIRATORY SYSTEM; TECHNETIUM ISOTOPES; TOMOGRAPHY; VERTEBRATES; YEARS LIVING RADIOISOTOPES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics

Citation Formats

Lisbona, R., Hakim, T.S., Dean, G.W., Langleben, D., Guerraty, A., and Levy, R.D. Regional pulmonary perfusion following human heart-lung transplantation. United States: N. p., 1989. Web.
Lisbona, R., Hakim, T.S., Dean, G.W., Langleben, D., Guerraty, A., & Levy, R.D. Regional pulmonary perfusion following human heart-lung transplantation. United States.
Lisbona, R., Hakim, T.S., Dean, G.W., Langleben, D., Guerraty, A., and Levy, R.D. 1989. "Regional pulmonary perfusion following human heart-lung transplantation". United States. doi:.
@article{osti_5672279,
title = {Regional pulmonary perfusion following human heart-lung transplantation},
author = {Lisbona, R. and Hakim, T.S. and Dean, G.W. and Langleben, D. and Guerraty, A. and Levy, R.D.},
abstractNote = {Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.},
doi = {},
journal = {Journal of Nuclear Medicine; (USA)},
number = ,
volume = 30:8,
place = {United States},
year = 1989,
month = 8
}
  • Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dosemore » data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong Foundation.« less
  • Recent studies suggest that cardiac uptake of {sup 111}In-labeled antimyosin monoclonal antibody may be estimated semiquantitatively by calculating a heart-to-lung activity ratio, with pulmonary uptake serving as a reference region. The authors obtained 96 {sup 111}In-antimyosin scintigraphs to monitor rejection occurrence after heart transplantation in 26 patients. On five scintigraphs, the count rate density in ROIs over the lungs was markedly higher (mean 53% higher) than that in the immediately preceding and following scintigraphs, whereas the activity in the heart was essentially unchanged. Four of these scintigraphs coincided with ongoing pulmonary infection and the fifth with an occurrence of amore » high anti-CMV titer. The mechanism of apparent nonspecific antimyosin accumulation in the lungs is uncertain, although increased capillary permeability may be one possibility. Attention should be given to activity in the lungs if this activity is used as a reference in studies of {sup 111}In-antimyosin uptake in the heart. 15 refs., 3 figs., 1 tab.« less
  • Research highlights: {yields} Addition of KAT Abs (+) sera to NHBE culture causes upregulation of growth factors. {yields} Cholesterol depletion causes down regulation of growth factor expression. {yields} Cholesterol depletion is accompanied by loss of membrane bound caveolin. {yields} Thus, we demonstrate lipid raft are critical for efficient ligation of the KAT Abs. -- Abstract: Long term function of human lung allografts is hindered by development of chronic rejection manifested as Bronchiolitis Obliterans Syndrome (BOS). We have previously identified the development of antibodies (Abs) following lung transplantation to K-{alpha}1-tubulin (KAT), an epithelial surface gap junction cytoskeletal protein, in patients whomore » develop BOS. However, the biochemical and molecular basis of the interactions and signaling cascades mediated by KAT Abs are yet to be defined. In this report, we investigated the biophysical basis of the epithelial cell membrane surface interaction between KAT and its specific Abs. Towards this, we analyzed the role of the lipid raft-domains in the membrane interactions which lead to cell signaling and ultimately increased growth factor expression. Normal human bronchial epithelial (NHBE) cells, upon specific ligation with Abs to KAT obtained either from the serum of BOS(+) patients or monoclonal KAT Abs, resulted in upregulation of growth factors VEGF, PDGF, and bFGF (6.4 {+-} 1.1-, 3.2 {+-} 0.9-, and 3.4 {+-} 1.1-fold increase, respectively) all of which are important in the pathogenesis of BOS. To define the role for lipid raft in augmenting surface interactions, we analyzed the changes in the growth factor expression pattern upon depletion and enrichment with lipid raft following the ligation of the epithelial cell membranes with Abs specific for KAT. NHBE cells cultured in the presence of {beta}-methyl cyclodextran ({beta}MCD) had significantly reduced growth factor expression (1.3 {+-} 0.3, vs {beta}MCD untreated being 6.4 {+-} 1.1-fold increase) upon stimulation with KAT Abs. Depletion of cholesterol on NHBE cells upon treatment with {beta}MCD also resulted in decreased partitioning of caveolin in the membrane fraction indicating a decrease in raft-domains. In conclusion, our results demonstrate an important role for lipid raft-mediated ligation of Abs to KAT on the epithelial cell membrane, which results in the upregulation of growth factor cascades involved in the pathogenesis of BOS following human lung transplantation.« less
  • Purpose: To quantitatively assess the in vivo acute vascular effects of fractionated radiotherapy for human non-small-cell lung cancer using volumetric perfusion computed tomography (CT). Methods and Materials: Sixteen patients with advanced non-small-cell lung cancer, undergoing palliative radiotherapy delivering 27 Gy in 6 fractions over 3 weeks, were scanned before treatment, and after the second (9 Gy), fourth (18 Gy), and sixth (27 Gy) radiation fraction. Using 16-detector CT, multiple sequential volumetric acquisitions were acquired after intravenous contrast agent injection. Measurements of vascular blood volume and permeability for the whole tumor volume were obtained. Vascular changes at the tumor periphery andmore » center were also measured. Results: At baseline, lung tumor vascularity was spatially heterogeneous with the tumor rim showing a higher vascular blood volume and permeability than the center. After the second, fourth, and sixth fractions of radiotherapy, vascular blood volume increased by 31.6% (paired t test, p = 0.10), 49.3% (p = 0.034), and 44.6% (p = 0.0012) respectively at the tumor rim, and 16.4% (p = 0.29), 19.9% (p = 0.029), and 4.0% (p = 0.0050) respectively at the center of the tumor. After the second, fourth, and sixth fractions of radiotherapy, vessel permeability increased by 18.4% (p = 0.022), 44.8% (p = 0.0048), and 20.5% (p = 0.25) at the tumor rim. The increase in permeability at the tumor center was not significant after radiotherapy. Conclusion: Fractionated radiotherapy increases tumor vascular blood volume and permeability in human non-small-cell lung cancer. We have established the spatial distribution of vascular changes after radiotherapy; greater vascular changes were demonstrated at the tumor rim compared with the center.« less