Proton-decoupled 31P chemical shift imaging of the human brain in normal volunteers

Proton-decoupled, 31P three-dimensional (3-D) chemical shift imaging (CSI) spectra have been acquired from the entire human brain using a new dual tuned resonator. The resonator operates in quadrature mode to provide improved sensitivity, excellent B1 homogeneity and reduced power deposition at both frequencies. Proton-decoupled and fully NOE enhanced, 31P spectra were acquired from normal volunteers using Waltz-4 proton decoupling with continuous wave bi-level excitation applied through a second radio frequency channel. Well resolved peaks in the phosphomonoester (PME) and phosphodiester regions were obtained from nonlocalized FIDs and spectra localized with 3-D CSI without processing for resolution enhancement. pH measurements made over large regions of the brain using the P(i) resonance show no significant variations (6.9 +/- 0.02) for a single individual. The improved spectral resolution and sensitivity of the PME resonances results in more well defined metabolite images of the PME peak region.     

Molar quantitation of hepatic metabolites in vivo in proton-decoupled, nuclear Overhauser effect enhanced 31P NMR spectra localized by three-dimensional chemical shift imaging

Proton decoupling and nuclear Overhauser effect (NOE) enhancement significantly improve the signal-to-noise ratio and enhance resolution of metabolites in in vivo 31P MRS. We obtained proton-decoupled, NOE-enhanced, phospholipid-saturated 31P spectra localized to defined regions within the normal liver using three-dimensional chemical shift imaging. Proton-decoupling resulted in the resolution of two major peaks in the phosphomonoester (PME) region, three peaks in the phosphodiester (PDE) region and a diphosphodiester peak. In order to obtain molar quantitation, we measured the NOE of all hepatic phosphorus resonances, and we corrected for saturation effects by measuring hepatic metabolite T1 using the variable nutation angle method with phase-cycled, B1-independent rotation, adiabatic pulses. After corrections for saturation effects, NOE enhancement, B1 variations and point spread effects, the following mean concentrations (mmol/l of liver) (+/-SD) were obtained: [PME1] = 1.2 +/- 0.4, [PME2 + 2,3-DPG] = 1.1 +/- 0.1, [Pi + 2,3-DPG] = 2.8 +/- 0.5, [GPEth] = 2.8 +/- 0.7, [GPChol] = 3.5 +/- 0.6 and [beta-NTP] = 3.8 +/- 0.3. T1 and NOE enhancement were strongly correlated (r = 90), and indicated that the fractional contribution of 1H-31P dipolar relaxation to total 31P relaxation is minimal for NTPs, moderate for PMEs and high for PDEs in liver. Proton-decoupling and NOE enhancement permit one to obtain more information about in vivo metabolism of liver than previously available and should enhance the utility of 31P MRS for the study of hepatic disorders.     

Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging

The imaging of regional ventilation in the lungs is essential for the evaluation of a variety of pathological conditions, such as emphysema, pneumonia and pulmonary embolism. We propose a novel approach for ventilation scanning, using magnetic resonance imaging (MRI) and inhaled molecular oxygen as a contrast agent, that directly depicts transfer of oxygen across the alveolus into the pulmonary vasculature. Molecular oxygen is only weakly paramagnetic but produces substantial signal changes in the lungs because of their large surface area. Ventilation defects were shown in a patient with bullous emphysema, and ventilation-perfusion mismatches were shown in two patients with pulmonary embolism.     

19F chemical shift imaging technique to measure intracellular pO2 in vivo using perflubron

RATIONALE AND OBJECTIVES: There is a linear relation between the T1 relaxation rate of fluorine-19 (19F) of perfluorochemicals (PFCs) and the partial pressure of the oxygen (pO2) dissolved in the PFC. A line scan technique was used to overcome the significant chemical shift and low signal-to-noise ratio (SNR) of in vivo 19F magnetic resonance imaging. This study was designed to determine whether the line scan technique could detect the effect of oxygen on 19F T1. In addition, its ability to detect changes in intracellular pO2 when the inspired gas was raised from 20% to 100% O2 also was investigated. METHODS: The T1 relaxation rate of samples of perflubron emulsion diluted from 3.5% to 70% w/v and equilibrated with N2-O2 gas mixtures (pO2 range = 10-450 mm Hg) was measured using the line scan technique. The gas and emulsion pO2 were measured with a blood gas analyzer. The liver T1 relaxation rate was measured in three rabbits given 5 ml/kg perflubron emulsion 4 and 8 days earlier as they breathed room air and then 100% O2. We used a prototype cylindrical coil double-tuned to hydrogen-1 (1H) and 19F and selected a line through the liver. The scanning parameters yielded a voxel size of 20 x 20 x 15.6 mm. Liver and blood samples were obtained postsacrifice for perflubron concentration measurement. RESULTS: A linear relation between the 19F T1 relaxation rate (1/T1) of the 3.5% w/v emulsion and dissolved pO2 was established with a slope of 0.0033 (sec-1/mm Hg) and a correlation coefficient of .991. As the PFC concentration increased by 1,900%, the slope increased by 21.2%. The 1/T1 for the liver was 0.182 +/- 0.004 sec-1 at baseline. It increased to 0.247 +/- 0.022 sec-1 when rabbits breathed 100% O2 (p = .023), which corresponded to an increase in intracellular pO2 of 19.7 mm Hg. The liver-to-blood PFC concentration ratio was 500:1. CONCLUSION: In vitro measurements with the line scan technique replicated the established linear dependence of 1/T1 on pO2. In vivo measurements indicated a 20-mm Hg increase in intracellular pO2 of liver phagocytes when the inspired gas was changed from 20% to 100% O2.     

Noninvasive hemodynamic assessment of the internal mammary artery in myocardial revascularization

Using transthoracic B-mode imaging and Doppler spectrum analysis it was found that the luminal diameter of the internal mammary artery and its hemodynamics were not significantly different among 15 preoperative patients (64 +/- 10 years) who underwent myocardial revascularization using the left internal mammary artery and young and older control groups (25 +/- 3 years and 61 +/- 9 years, respectively). These data indicate that older age does not significantly adversely influence the degree of intimal thickening and compliance in the internal mammary artery. Doppler spectrum analysis of the internal mammary artery in the patients who were operated on revealed conversion from a triphasic systolic waveform preoperatively to a unidirectional combined systolic/diastolic waveform at 1 week and 2 and 6 months postoperatively, characterized by a significant increase in the diastolic blood flow velocity and a significant decrease in the systolic blood flow velocity and the pulsatility and resistance indices. This study indicates that transthoracic B-mode imaging and Doppler spectrum analysis are promising noninvasive techniques in the preoperative assessment of internal mammary artery morphology and physiology. In addition, Doppler spectrum analysis can also be used in the long-term serial assessment of the internal mammary artery conduit after myocardial revascularization.     

Calibration of water proton chemical shift with temperature for noninvasive temperature imaging during focused ultrasound surgery

Long-standing ulcerative colitis is considered to be a precancerous condition. Therefore, a practical and reliable method is required for monitoring the progress of the disease. Liberation of the S-phase from karyokinesis occurs in DNA amplification and endoreplication, producing nuclei with more than 4 c DNA. The amount of Feulgen DNA was quantified with an image microphotometer in 8 microns sections for interphase nuclei and in 15 microns sections for chromosome division figures (CDFs). Development of ulcerative colitis was investigated in low grade dysplasia (n = 93 cases; score 3-7) and high grade dysplasia (n = 22; score 8-10). Bacterial colitis (n = 34) and invasive adenocarcinoma (n = 26) provided a basis for data interpretation in dysplasia. Lymphocyte nuclei served as an internal DNA standard. CDFs represent a novel type of aberrant 'mitoses'; they are different from and much more frequent than figures with multipolar spindles. Endoreplication began with low grade dysplasia in interphase nuclei as well as with CDFs; it was fully established in high grade dysplasia and carcinoma. Endoreplicated interphase nuclei and CDFs represent an early morphological mosaic of genomic instability. Both characteristics support a reproducible two-level classification of low and high grade dysplasia in ulcerative colitis.     

In vivo study of halothane hepatotoxicity in the rat using magnetic resonance imaging and 31P spectroscopy

Using magnetic resonance imaging (MRI) and spectroscopy (MRS), in vivo halothane hepatotoxicity was assessed in male Wistar rats. With 1.5% halothane in 100 or 20% O2, an edematous region, characterized by increased intensity on T2 weighted images and an increase in regional tissue water content (rho water), was seen proximal to the hepatic portal vein in the liver. Both spin-lattice relaxation (T1) and spin-spin relaxation (T2) increased in this region, relative to distal regions of the liver. Similarly, a high signal intensity on proton density weighted images was observed in this area. As halothane anaesthesia progressed, a decrease in the adenosine triphosphate-inorganic phosphate ratio (ATP/Pi) and an increase in the phosphomonoester-phosphodiester (PME/PDE) ratio was detected in the liver. In addition, intracellular pH decreased and intracellular free magnesium concentration [Mg2+] increased with time of exposure. Excessive vacuolation, ribosomal disappearance from rough endoplasmic reticulum, mitochondrial swelling and fragmentation of smooth endoplasmic reticulum were observed by transmission electron microscopy (TEM) in samples from the edematous region of the liver.     

Quantitation of lipid in biological tissue by chemical shift magnetic resonance imaging

A method combining several previously used approaches is described for the rapid, accurate quantitation of the fat content of biological tissue based on chemical shift images (CSI) corrected for magnetic field inhomogeneity, and compensated for T1 and T2 effects. The gravimetrically determined lipid content of fatty tissues (pork fat, rabbit and human liver) that had been differentially depleted of lipid by chloroform extraction correlated well (r = 0.99) with the lipid image intensities of the respective tissues. This multi-point CSI method was used to quantitate lipid in fresh fatty human liver tissue (wet and dry) containing varying amounts of lipid. Plots of integrated lipid intensity versus tissue lipid content gave straight parallel lines for hydrated (r = 0.94) and dehydrated (r = 0.98) tissues, permitting determination of a proportionality constant for measuring absolute amounts of lipid present in a specific biological tissue. These results suggest the feasibility of using the method in vivo for absolute quantitation of lipid in tissues of agricultural (e.g. pork, beef) and medical (e.g. human liver) interest.     

Heteronuclear NMR studies of cobalt corrinoids. 20. 31P chemical shift anisotropy of aquacobalamin and its complex with a haptocorrin from chicken serum

Static light scattering measurements have been used to determine the molecular mass (65.3 kDa) and second virial coefficient (3.66 x 10(-4) mol mL g-2) for the complex between chicken serum haptocorrin (HC) and aquacobalamin (H2OCbl). Dynamic light scattering measurements have also been used to determine the translational diffusion coefficient of the H2OCbl-HC complex as a function of concentration. From the diffusion coefficient at infinite dilution (4.71 x 10(-7) cm2 s-1), the hydrodynamic radius (45.5 A) and rotational correlation time (85.4 ns) have been calculated. Using the latter, and measured values of the 31P NMR linewidths of the H2OCbl-HC complex at several field strengths, a detailed analysis of the 31P nuclear relaxation is possible. The chemical shift anisotropy term from the transverse relaxation equation is determined to be 95.7 ppm, and the average phosphorus-proton internuclear distance is 2.05 A. For comparison to protein-free H2OCbl, the chemical shift anisotropy of the phosphorus atom was studied by solid state NMR spectroscopy and the 31P relaxation by solution T1 measurements. These studies give values of 110.3 ppm for the chemical shift anisotropy term and 2.45 A for the average phosphorus-proton internuclear distance. The results are consistent with a significant change in the conformation of the H2OCbl phosphodiester upon binding to haptocorrin which could be due to a shortening of the axial Co-N bond.     

Spatially localized 31P NMR measurements of longitudinal relaxation rates in the canine myocardium

FLAX-ISIS spatial localization was combined with inversion recovery to enable the measurement of spatially localized T1 values. This approach was applied to the transmural determination of creatine phosphate longitudinal relaxation times in the canine myocardium. By examining five voxels spanning the left myocardial wall, we observed that transmural T1 values for creatine phosphate ranged from 3.61 +/- 0.20 in the endocardium to 4.00 +/- 0.20 in the epicardium at 4.7 Tesla. As such, the canine myocardium exhibits no transmural variation in the T1 values of creatine phosphate. This simple approach can be extended to enable the in vivo measurement of transmural enzymatic rates.     

Integrated MRI assessment of regional function and perfusion in canine myocardial infarction

A single integrated examination using regional measurements of perfusion from contrast-enhanced MRI and three-dimensional (3D) strain from tissue-tagged MRI was developed to differentiate infarcted myocardium from adjacent tissue with functional abnormalities. Ten dogs were studied at baseline and 10 days after a 2-hour occlusion of the left anterior descending coronary artery (LAD). Strain was determined using a 3D finite element model. Two-dimensional measurements of hypoenhancing regions were highly correlated with myocardial viability (r = 0.96). Signal intensity versus time curves obtained from contrast-enhanced MRI were used for quantitative perfusion analysis. The remote and adjacent noninfarcted tissue of the dogs with LAD occlusion, as well as the infarcted tissue, exhibited abnormal deformation patterns as compared to normal dogs (positive predictive value (PPV) of strain determination of infarction = 66%). Integration of contrast-enhanced MRI results with 3D strain analysis enabled the delineation of the myocardial infarction (PPV = 100%) from functionally compromised myocardium. This integrated cardiac examination shows promise for noninvasive serial assessment of potentially jeopardized noninfarcted myocardium to study the process of infarct remodeling and expansion.     

Choice of soft pulse shapes for signal excitation in chemical shift selective imaging

The choice of soft pulse shapes for chemical shift selective excitation in chemical shift imaging is discussed. In the presence of inhomogeneities in the static magnetic field resulting from susceptibility anomalies, it is important to optimise pulse bandshape and frequency offset as well as bandwidth, in order to minimize artefacts arising from excitation of unwanted resonances. A comparison of the use of Gaussian and sinc shaped excitation pulses in the chemical shift micro-imaging of grapes serves to illustrate some of the effects that may be observed.     

Comparison of iodine-123-disintegrins for imaging thrombi and emboli in a canine model

Disintegrins are peptides found in viper venoms which bind to platelets through the glycoprotein IIb-IIIa receptor. The purpose of this work was to evaluate the ability of disintegrins to image thrombi and emboli in vivo. METHODS: Eight disintegrins (bitistatin, albolabrin, echistatin, eristostatin, kistrin, mambin, halysin and barbourin) were purified from snake venom. After radiolabeling with 123I, disintegrins were tested for their ability to image 24-hr-old experimental deep vein thrombi (DVT) and pulmonary emboli in a canine model. Labeled fibrinogen and platelets were used as controls. Gamma camera imaging was performed during the first 4 hr, after which tissue samples were collected for counting. RESULTS: Of the disintegrins tested, 123I-bitistatin had higher uptake in DVT (0.21 +/- .06% ID/g) than any other disintegrin (0.009-0.036%/g, p < 0.05). Bitistatin had higher DVT-to-blood ratios (9.8 +/- 2.5) than all other disintegrins, 125I-fibrinogen or 99mTc-HMPAO-platelets (p < 0.05). Images of DVT obtained with 123I-bitistatin were focally positive within 1 hr and improved by 4 hr. In pulmonary emboli, the absolute uptake of 123I-bitistatin (0.64 +/- 0.17% ID/g) was higher than all other compounds (p < 0.05), although barbourin had moderate uptake (0.23 +/- 0.11% ID/g) and may also be useful for imaging pulmonary embolism (PE). The uptake of bitistatin in PE was superior to both 125I-fibrinogen (0.18 +/- 0.02% ID/g) (p < 0.05) and 99mTc-HMPAO-platelets (0.14 +/- 0.02% ID/g, p < 0.05). Iodine-123-bitistatin had embolus-to-blood ratios averaging 27 +/- 7, which was higher than platelets, fibrinogen, echistatin, mambin or halysin (p < 0.05). Iodine-123-bitistatin background in lungs, liver and heart were low, which permitted visualization of all pulmonary emboli by 2-4 hr after injection. CONCLUSION: Labeled bitistatin should be investigated further as an agent which may permit rapid imaging of both thrombi and emboli.     

Scintigraphic assessment of silent myocardial ischaemia after early infarction using myocardial SPET imaging with 201Tl and 123I-MIBG

To test the hypothesis that myocardial sympathetic denervation reflects silent myocardial ischaemia early after infarction, 12 patients with myocardial infarction but without post-infarction angina pectoris underwent single photon emission tomography (SPET) at rest with 201Tl and 123I-metaiodobenzylguanidine (MIBG) shortly after and 3 months after infarction. Short-axis SPET images at the basal, mid-ventricular and apical portions of the left ventricle were selected, and each short-axis image was divided into eight segments. Tracer uptake in each of the 24 segments was scored using a 4-point scale. The total score in each segment was calculated as the defect score for each image, and the difference between the total defect score for the 201Tl and 123I-MIBG images was calculated as the delta defect score. All 12 patients underwent exercise stress 201Tl scintigraphy 1 month after infarction, and they were divided into two groups: those patients with (Group A, n = 7) and those patients without (Group B, n = 5) transient perfusion defects in the peri-infarcted region without chest pain. For the 123I-MIBG defect score, a marked reduction at 3 months was observed in Group A (24 +/- 12 vs 13 +/- 6; P < 0.01), whereas the defect score remained unchanged in Group B (25 +/- 7 vs 23 +/- 8; N.S.). The delta defect score was significantly reduced in Group A (10 +/- 5 vs 6 +/- 4; P < 0.05), whereas it remained unchanged in Group B. The 123I-MIBG defect score early after infarction was higher than the exercise-induced 201Tl defect score (24 +/- 12 vs 20 +/- 9; P < 0.01), whereas at 3 months post-infarction it was lower than the exercise-induced 201Tl defect score (13 +/- 6 vs 20 +/- 9; P < 0.05). Moreover, effort chest pain during daily activities was noted in 5 of the 7 (71%) patients in Group A within 3 months post-infarction. The results of this study suggest that viable but denervated myocardium (mismatched 123I-MIBG defects) is present in peri-infarcted regions, and that myocardial sensory nervous disturbance, which may co-exist with sympathetic nervous denervation, may induce silent myocardial ischaemia in patients with myocardial infarction.     

Effect of ethanol on myocardial infarct size in a canine model of coronary artery occlusion-reperfusion

INTRODUCTION: We investigated the effectiveness of Levovist (SHU508A, Schering AG, Berlin, Germany) in the characterization of breast lesions. MATERIAL AND METHODS: June, 1996, to May, 1997, we studied 29 solid lesions in 29 patients (aged 17 to 83 years); our patients were 28 women and 1 man. The 29 solid lesions were 20 carcinomas (15 infiltrating ductal carcinomas, 4 ductal carcinomas in situ, 1 lobular carcinoma in situ), 6 fibroadenomas, 1 suspected postoperative recurrence and 2 apparently benign lesions. We used parameters suitable for the study of slow flows. A single bolus of contrast agent (300 mg/mL) was administered at 1-2 mL/s. Before Levovist injection, we studied the lesion signal intensity and the number of vascular poles. After contrast administration we re-evaluated both these parameters and studied the changes or presence of vessels undetected on the previous images. We also investigated the beginning and duration of enhancement and the presence of vessels inside and outside the lesions. RESULTS: We observed no signal enhancement in 17% of cases, mild enhancement in 7% and strong enhancement in 76% of cases. We found 3 more vascular poles (17%) in 5 lesions and 4 more poles in 3 lesions (10%). Increased vascularization was seen inside the lesion in 17% of cases, inside and outside it in 41% and only outside in 35% of cases. Carcinomas showed a rapid and long-lasting enhancement, while fibroadenomas showed a later and weaker enhancement. CONCLUSIONS: Levovist can be useful in the differential diagnosis of benign from malignant lesions, of recurrences from postoperative fibrosis, as well as in the staging and follow-up of the patients treated with neoadjuvant chemotherapy.     

Reproducibility of polar map generation and assessment of defect severity and extent assessment in myocardial perfusion imaging using positron emission tomography

The intestinal tract has many features that make it an attractive target for therapeutic gene transfer. In this study, replication-defective adenoviral vectors were used to explore parameters that may be important in administering gene therapy vectors to the intestine. After surgically accessing the intestine, an E1-, E3-deleted adenoviral vector encoding beta-galactosidase (beta-Gal) was directly injected into various regions of the small and large intestine of rats and rabbits. Significant transduction of the tissue was observed and histochemical staining was used to identify enterocytes as the primary targets of gene transfer. Expression of beta-Gal did not differ substantially when the virus was administered to the duodenum, ileum, or colon. When the vector was directly administered to segments of the distal ileum containing a Peyer's patch, transgene expression was approximately 10-fold higher than in segments lacking a Peyer's patch. In the Peyer's patches, a high level of expression was localized to epithelial cells, potentially M cells, overlying the lymphoid follicle domes. Transduction of these cells could have application in DNA-mediated oral vaccination. Administration of an adenoviral vector encoding a secreted alkaline phosphatase to the lumen resulted in expression and secretion of this gene product into the circulation. This finding demonstrates the potential of enterocytes to serve as heterotopic sites for the synthesis of heterologous gene products that would be secreted into the lumen of the intestinal tract or into the bloodstream.     

Effect of dietary supplementation with zinc sulphate on the aging process: a study using high field intensity MRI and chemical shift imaging

High field intensity magnetic resonance imaging (HF-MRI) has been applied to the in vivo study of age-related processes of organs located in the cervical-thoracic region in mice and to describe the effects of oral zinc supplementation on these processes. Spin-echo (SE) pulse sequence and chemical shift imaging (CSI) techniques have been used. Aging produced a progressive reduction of muscular masses and of thymic area, whereas the HF-MRI appearances of spinal cord and of salivary glands were unchanged. In some aged animals, subcutaneous fat was reduced while visceral fat was well developed. In the group of old animals supplemented with zinc sulphate, muscular masses were more developed than that of the group of untreated old animals. Oral zinc supplementation also produced an enlargement of the adipose tissue and the thymic area showed an increase of about 65% compared with thymic area measured in the group of old animals used as controls. The present study confirms previous data about the effects of Zn supplementation on aging processes and demonstrates that HF-MRI is a powerful technique to study processes of aging, providing information about the effects of drug treatments on these processes.     

Prediction of properties of intermetallics using a chemical bonding model

Materials with novel properties are needed for new technology developments. It is important to be able to predict which of the millions of multicomponent intermetallics might provide the desired properties. A single chemical bonding model, the Brewer-Engel, has provided reliable thermodynamic data for the metallic elements in a variety of crystal structures. The model can be extended to intermetallics. An illustration of the calculations is available for Al or Mg with transition metals forming intermetallics with binary CsCl structures. A number of publications will be available for similar calculations for a variety of crystal structures. The calculations will be extended to a variety of compositions and multicomponent systems. The present article will discuss the procedures that can be used to simplify the calculations, yet maintain reliable accuracy. This article is based on a presentation made at “The Milton Blander Symposium on Thermodynamic Predictions and Applications” at the TMS Annual Meeting in San Diego, California, on March 1–2, 1999, under the auspices of the TMS Extraction and Processing Division and the ASM Thermodynamics and Phase Equilibrium Committee.     

Inhibition of lipid peroxidation with the lazaroid U74500A attenuates ischemia-reperfusion injury in a canine orthotopic heart transplantation model

BACKGROUND: The lazaroid U74500A is a 21-aminosteroid that inhibits lipid peroxidation and attenuates ischemia-reperfusion injury. We examined the effect of U74500A on heart preservation with the use of a clinically relevant canine orthotopic heart transplantation model. METHODS AND RESULTS: Six donor dogs (group L) were pretreated intravenously with U74500A (10 mg/kg), and the dogs without pretreatment served as a control (group C, n = 6). The donor heart was preserved in cold University of Wisconsin solution for 24 hours. The heart was then transplanted orthotopically. Myocardial biopsy was performed to measure the adenosine triphosphate level at the end of ischemia. Before reperfusion, recipients in group L received another dose of U74500A (10 mg/kg) intravenously. After 3 hours of reperfusion, left ventricular function was evaluated by left ventricular pressure-volume relations with the use of a Millar catheter and conductance catheter, thereby deriving the slope of the end-systolic pressure-volume relation, the slope of the stroke work-- end-diastolic volume relation, and the slope of the maximum dP/dt--end-diastolic volume relation. At the same time, serum creatine kinase MB isoenzyme and lipid peroxide levels were measured. The slopes of the end-systolic pressure-volume relation, the stroke work--end-diastolic volume relation, and the maximum dP/dt--end-diastolic volume relation for group L were significantly higher than those for group C. The adenosine triphosphate levels for group L were significantly higher than those for group C. Serum creatine kinase MB isoenzyme and lipid peroxide levels for group L were significantly lower than those for group C. CONCLUSIONS: Inhibition of lipid peroxidation by the administration of U74500A was effective for 24-hour canine cardiac preservation. These results indicate that U74500A is a promising agent for heart allograft preservation.     

Improved airway healing using basic fibroblast growth factor in a canine tracheal autotransplantation model

OBJECTIVE: We studied 22 dogs to examine the effect of basic fibroblast growth factor (bFGF) alone, in comparison with omental or muscular wrapping on airway healing in a tracheal autotransplantation model. SUMMARY BACKGROUND DATA: Basic fibroblast growth factor is one of the most potent promoters of angiogenesis and has an ability to enhance blood supply to the ischemic airway. Topical administration of a fibrin glue enriched with 5 microg/cm2 bFGF, determined as a proportion of surface area of the tracheal grafts, improved revascularization of orthotopic canine tracheal autografts in a previous study. METHODS: All animals received orthotopic tracheal transplantation using 6-ring autografts that occupied a distal part of the thoracic trachea. Twenty-two animals were classified randomly into the following four groups: no treatment (Group G1, n = 4), muscular wrapping (Group G2, n = 4), omental wrapping (Group G3, n = 4), and topical administration of fibrin glue enriched with 5 microg/cm2 bFGF (Group G4, n = 10). Autografts were harvested 60 days after transplantation and assessed by the percent patency and histology. RESULTS: Devascularized tracheal autografts could not maintain their structural integrity without other treatments (Group G1). In contrast, more than half of all autografts receiving treatments remained viable, as demonstrated by gross and histologic findings (Groups G2, G3, and G4). Treatments with bFGF and omentum showed significantly better graft viability than no treatment. However, there was no statistical difference in the viability of tracheal autografts among the three treatment groups. In terms of the time performance ratio, bFGF was the best treatment for the devascularized autografts. CONCLUSIONS: Topical administration of bFGF was superior to the omental or muscular wrapping in terms of the time performance ratio. Clinical trials will be necessary to determine whether these findings are applicable to humans.