Transient cold preservation alone stimulates tumor necrosis factor-alpha gene expression in a model of rat syngeneic lung transplantation.
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Animals↗
Biomedical subjects
J Matloff
Publications and source records attributed to J Matloff.
Prolongation of skin allograft survival is associated with reduced Th1 cytokine responses in the WKY-->F344 rat model.
BACKGROUND: We have reported previously that F344 rats develop a spontaneous tolerance to WKY lung allografts and show long-term retention of donor-specific skin grafts placed 35 days after lung transplantation. In this study, we investigated the immunologic mechanisms that may be responsible for the prolonged skin graft survival in animals tolerized with lung allografts. METHODS: In the rejection group, WKY skin grafts were placed on normal F344 rats, whereas, in the tolerance group, the skin grafts were placed on F344 rats that had received a WKY lung transplant 35 days before skin grafting. Th1 (interleukin [IL]-2 and interferon-gamma [IFN-gamma]) and Th2 (IL-4 and IL-10) cytokine as well as transforming growth factor-beta1 mRNA expression in skin grafts and in draining lymph nodes were determined by reverse transcription-polymerase chain reaction. Macrophage and lymphocyte infiltration in skin grafts and the number of Langerhans cells in epidermal sheets of the grafts were examined by immunohistochemistry. RESULTS: IL-2 and IFN-gamma mRNA expression was significantly decreased in both the skin grafts and the draining lymph nodes of the tolerance group, compared to the rejection group, whereas IL-10 and transforming growth factor-beta1 mRNA expression was similar in both groups and IL-4 mRNA was rarely detected. Decreased and delayed CD8+, macrophage, and natural killer cell infiltration in the skin grafts from the tolerance group was also detected. Similar reduction in the number of Langerhans cells in the epidermis of the grafts from both groups was seen on day 1 after skin grafting, and thereafter the number remained stable in both groups. CONCLUSIONS: Reduced expression of Th1 cytokines and decreased infiltration of CD8+ cells, macrophages, and natural killer cells in the skin grafts may be responsible for prolongation of skin graft survival in the tolerance group.
Animals↗
Donor-specific transfusions enhance the immunosuppressive effects of single-dose cyclosporine A and CTLA4-Ig but do not result in long-term graft acceptance in a histoincompatible model of rat lung allograft rejection.
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Abatacept↗
Cytokine gene expression in rejecting and tolerant rat lung allograft models: analysis by RT-PCR.
UNLABELLED: Cytokine gene expression is a critical component of the lung allograft rejection (AR) response and tolerance development in rat models. In order to determine the specificity of cytokine gene expression for AR and tolerance, we examined cytokine (interleukin-2) (IL-2), (gamma-interferon) (gamma-IFN), IL-4, IL-10 and tumor necrosis factor-alpha (TNF-alpha) and control (cyclophilin) mRNA levels in two models of rat lung allograft rejection by RT-PCR (reverse transcriptase polymerase chain reaction), Southern blotting. The first model (WKY-->F344) develops a mild to moderate lymphocytic infiltrate on days 14-21 post-transplant (stage II-III AR), which spontaneously resolves by day 35 post-transplant with subsequent development of allograft tolerance (grafts surviving without evidence of AR for > 140 days). Conversely, F344-->WKY develops a similar lymphocytic infiltrate by day 14 post-transplant, but by day 21 post-transplant the graft shows severe AR (stage III-IV) and has haemorrhagic infarction with alveolar haemorrhage. METHODS: RNA was extracted from allografts removed on days 3, 7, 14, 21, 35 and 42 post-transplant. Five animals for each group (WKY-->F344) and F344-->WKY) were examined at each time point, except that no animals in the F344-->WKY were examined on day 42. cDNA was synthesized from total extracted RNA and primers specific for rat TNF-alpha, rat IL-2, rat gamma-IFN, rat IL-4, rat-IL-10 and rat cyclophilin were used for gene-specific amplification. (TNF-alpha, gamma-IFN, IL-10, 20 cycles; IL-2, IL-4, 30 cycles; cyclophilin, 20 cycles). The cycles numbers chosen for comparison were found to be optimal during preliminary experiments and occurred during the exponential phase of amplification. PCR products were electrophoresed on a polyacrylamide gel and silver-stained. Gels were subsequently electrotransferred to nylon membranes which were probed with murine cDNAs specific for IL-2, gamma-IFN IL-4, IL-10 and TNF-gamma. RESULTS: Cyclophilin gene expression was similar for both models at all time points tested; this also served as an internal standard for RT-PCR. In the WKY-->F344 tolerance model, TNF-alpha mRNA levels were not detectable on days 3 and 7 post-transplant, were at very low levels on day 14 and were undetectable on day 21 post-transplant. In marked contrast, the F344-->WKY rejection model showed TNF-alpha mRNA present on day 3 which increased markedly on day 7 and peaked on day 14 post-transplant. TNF-alpha mRNA levels decreased on days 21 and 35 post-transplant, a time when the lung was undergoing AR. The pattern of IL-2 and gamma-IFN mRNA expression was similar to that for TNF-alpha. However, IL-2 mRNA was clearly detectable in the WKY-->F344 tolerance model on day 7 and gamma-IFN was not present until day 14 post-transplant. The F344-->WKY rejection model showed very high levels of IL-2 and gamma-IFN on day 3 which peaked on day 14. The ratio of IL-2/IL-10 in the F344-->WKY rejection model was more than 5 times that seen in the WKY-->F344 tolerance model on day 3 (p < 0.0005). The ratio of IL-2/IL-4 was higher (1.5 times) in the F344-->WKY rejection model than in the WKY-->F344 tolerance model (p < 0.007) on day 3. On day 14 post-transplant, the IL-2/IL-10 ratio in the F344-->WKY rejection model was three times that of the tolerance model (p < 0.0015). The IL-2/IL-4 ratio was 3.5 times greater in the WKY-->F344 tolerance model than in the rejectin model (p < 0.003). This was due to equal expression of IL-2 and IL-4 in the rejection model, but poor IL-4 expression in the tolerance model. CONCLUSIONS: 1) The WKY-->F344 tolerance model develops mild to moderate lymphocytic infiltrates on day 14 which is associated with low level IL-2, gamma-IFN and TNF-alpha gene expression. IL-10 and IL-4 are present at day 3; however, by day 14, IL-10 is the predominantly expressed Th2 cytokine and IL-4 is not expressed. The infiltrates ultimately resolve and the animals develop a functional tolerance to their grafts.4
Animals↗
Soluble CTLA4Ig modifies acute rejection of rat lung allografts without blocking accumulation of key cytokine transcripts.
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Abatacept↗
Orthotopic heart transplantation with bicaval and pulmonary venous anastomoses.
We present our experience with an alternative technique for orthotopic heart transplantation. It consists of total excision of the recipient's atria, with the donor's heart implantation performed using bicaval end-to-end anastomoses as well as pulmonary venous anastomoses. Forty consecutive patients receiving transplants in this fashion were compared with 64 patients who underwent orthotopic transplantation with the standard technique. The incidence of postoperative tricuspid regurgitation was reduced in patients receiving transplants with the new surgical approach (p = 0.003). In addition, the need for pacemaker implantation for severe bradyarrhythmia in the early (0 to 6 weeks) posttransplantation period (p = 0.003) was eliminated. Although not statistically significant, there was a trend in the reduction of postoperative mitral regurgitation in patients who received transplants by the modified technique. Based on this experience, we believe this modified technique for orthotopic heart transplantation has an anatomic and physiologic advantage that may improve long-term hemodynamic results.
Anastomosis, Surgical↗
High-efficiency gene transfer to autologous rabbit jugular vein grafts using adenovirus-transferrin/polylysine-DNA complexes.
Within the first year, 15-20% of coronary artery saphenous bypass vein grafts (SVGs) occlude because of thrombosis or progressive intimal hyperplasia. One potential new strategy to reduce this complication would be to introduce antithrombotic or antiproliferative genes in vein grafts before implantation. The success of this approach requires an efficient DNA delivery system. In the present study we tested the feasibility of using adenovirus-transferrin/polylysine-DNA complexes (TfAdpl/DNA) to achieve high-efficiency gene transfer into vascular interposition vein grafts. All studies used the Escherichia coli LacZ (beta-galactosidase [beta-Gal]) reporter gene under the control of the cytomegalovirus (CMV) earlier promoter and enhancer (pCMV/LacZ). Autologous rabbit jugular vein segments were incubated ex vivo for 60 min in a solution of TfAdpl/DNA complexes (1.2 x 10(10) biotinylated adenovirus particles, 2,430 ng of streptavindylated polylysine. 10 micrograms of plasmid DNA, and 9 micrograms of transferrin-polylysine per ml), and then reimplanted across the ligated right carotid artery. Control veins were incubated in TfAdpl solution in which DNA was omitted. A total of six grafts were treated with TfAdpl/DNA, and two grafts were treated with TfAdpl. Veins were harvested 3 (n = 3) and 7 (n = 3) days later and beta-Gal activity was determined by X-Gal chromogen staining. All six TfAdpl/DNA-treated grafts stained intensely blue, whereas control grafts were negative. Microscopic examination of serial sections revealed intracellular blue granules consistent with beta-Gal activity to be present in all of the endothelial cells and in numerous medial and advential cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoviridae↗
The St. Jude Medical valve. Experience with 1,000 cases.
We analyzed the long-term results of valve replacement with the St. Jude Medical bileaflet valve (St. Jude Medical, Inc., St. Paul, Minn.) in our first 1000 implantations between 1978 and 1992. A total of 399 patients had mitral valve replacement, 471 aortic valve, and 130 double (mitral and aortic) valve replacement. The average patient age was 64 +/- 15 years and the majority of patients (52%) had concomitant coronary disease. With 4328 patient-years of follow-up, 83% of the mitral group, 76% of the aortic group, and 77% of the double valve group were free of thromboembolism at 10 years after operation, and 87% of the mitral group, 82% of the aortic group, and 85% of the double valve group were free of valve-related hemorrhage. At 10 years, 91% of the mitral group, 84% of the aortic group, and 84% of the double valve group were free of valve-related death. However, overall survival at 10 years was only 42% +/- 4% for the mitral group, 43% +/- 4% for the aortic group, and 43% +/- 6% for the double valve group. For all three groups, age was a highly significant factor stratifying survival (p < 0.001), as was the presence of coronary disease (all p < 0.001). The excellent freedom from valve-related death at 10 years of 84% to 91% is in striking contrast to the overall survivals of 42% to 43% at 10 years. This difference suggests that the primary factors limiting long-term survival after valve replacement with the St. Jude Medical valve are not valve-related factors, but other patient factors such as age and concomitant coronary disease.
Aged↗
The participation of tumor necrosis factor in the pathogenesis of lung allograft rejection in the rat.
Tumor necrosis factor alpha and beta are polypeptide cytokines with a wide range of metabolic, immunologic, and inflammatory activities. TNF is known to participate in immune mediated injury of native lungs, but a role for TNF in mediating lung allograft rejection (AR) has not been established. In experiments reported here, we assessed the role of TNF in mediating lung AR in a rat model of lung transplantation (BN-->Lew) (RT1n-->RT1l). This model shows florid AR with all grafts completely destroyed by day 6 posttransplant. Graft pathology is characterized by massive lymphocytic infiltrates and hemorrhagic necrosis. Initially, 5 lung allograft recipients in each group were sacrificed on days 1 to 6 posttransplant. Allografts were removed, mRNA isolated, and Northern blotting or RT-PCR performed with blots probed with cDNAs or oligos specific for rat TNF-alpha cyclophylin and gamma-actin. Data were compared with syngeneic transplants (Lew-->Lew) and with normal controls. In addition, frozen lung allograft tissue was examined by indirect immunofluorescence, using antibodies specific for TNF. TNF-alpha mRNA levels were detectable on day 2 posttransplant, and peaked on days 6-7 posttransplant. IF studies showed TNF protein expression in mononuclear cells of rejecting allografts on day 3, peaking on day 6. Both TNF-alpha mRNA and protein levels correlated with maximal AR and hemorrhagic necrosis of grafts. Minimal TNF-alpha mRNA or protein was detected in syngeneic grafts or in contralateral native lungs. We then examined the ability of a rabbit polyclonal anti-TNF-alpha (7000 U/day) and anti-TNF-beta (5000 U/day) with 30% crossreactivity with rat TNF to modify the AR response. For each group, 4-5 left lung transplants were performed as described, and animals treated with anti-TNF-alpha, anti-TNF-beta, (anti-TNF-alpha+anti-TNF-beta) or with preimmune rabbit sera. All animals were sacrificed on day 6 posttransplant. Several pathological categories of inflammation were examined and scored (0-4), with a score of 0 = 0% involvement; 1 = 1-25% involvement; 2 = 26-50% involvement; 3 = 51-75% involvement; and 4 = 76-100% involvement. The mean and SD scores were obtained for all animals in the treatment categories mentioned above, and compared with preimmune-treated controls. Briefly, no differences in perivascular, peribronchial, or peribronchiolar cell infiltrates or edema were seen in treatment groups compared with controls.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
IMA-graft patency control by thermal coronary angiography during coronary bypass surgery.
Thermal coronary angiography (TCA) was evaluated for the intraoperative assessment of graft patency and flow in internal mammary artery (IMA) bypass grafts. TCA was performed in 210 patients undergoing 460 vein and 153 IMA bypass grafts after completion of the distal anastomoses. The IMA grafts and the recipient coronary arteries were delineated by the temperature differential between a cold epimyocardium and the perfusing warm blood after bulldog clamp release. TCA provided information about graft and anastomosis patency, initial flow patterns, and native coronary stenoses. TCA was performed in all studied IMA bypass grafts: 142 grafts were patent. Low flow but patency was observed in 24 IMA grafts and 11 IMA grafts showed no flow. Subsequently, 8 anastomotic failures and 3 proximal IMA graft occlusions were encountered. Based on these findings, 8 anastomoses were successfully revised and 7 additional vein grafts were added. One low flow IMA graft was not revised leading to postoperative ST elevation. Thirty-one distal native coronary stenoses were detected in the recipient LADs, 3 of which were not seen in the preoperative cineangiogram. In 20 instances, TCAs were obscured by an excess of fat or myocardium impeding image analysis. In 8 cases, TCA results were confirmed by conventional angiography postoperatively showing an excellent correlation in all cases. We conclude that intraoperative TCA demonstrates early IMA graft function and initial flow patterns. During our study, TCA documented a 7.2% IMA graft early failure rate. Intraoperative decision making was aided by TCA in 9.2% of all IMA grafts; this confirmed the clinical relevance of TCA.
Adult↗
Increased mortality of women in coronary artery bypass surgery: evidence for referral bias.
STUDY OBJECTIVE: To determine whether differences in referral reasons explain the higher operative mortality of women in coronary artery bypass surgery. DESIGN: Case series. SETTING: A tertiary care, private teaching hospital. PATIENTS: Consecutive patients who had isolated coronary artery bypass surgery between 1982 and 1987 (total, 2297; 79% male and 21% female). MEASUREMENTS AND MAIN RESULTS: The inhospital mortality rate was significantly higher for women than for men (4.6% compared with 2.6%; P = 0.036; 95% CI for difference in mortality, 0% to 4.0%). Women were older than men (mean, 68.2 and 64.0 years, respectively; P less than 0.001), and a higher percentage of women were referred with unstable angina (P = 0.007), postmyocardial infarction angina (P = 0.029), congestive heart failure (P less than 0.001), and New York Heart Association class IV symptoms (66% compared with 45%, P less than 0.001). More men were referred with a history of an abnormal exercise test (P less than 0.001), and patients referred because of a positive exercise test had a lower mortality (P less than 0.001). Using multivariate analysis, adjustment for the higher preoperative functional class of women and for age accounted for all of the difference in mortality between men and women (odds ratio, 1.04; CI, 0.60 to 1.79; P = 0.89). After correction for functional class alone, there continued to be no significant difference in mortality between men and women (P = 0.40). CONCLUSIONS: Differences in functional class and age account for the higher operative mortality of women in coronary bypass surgery. Women are referred for coronary bypass surgery later in the course of their disease than men, and later referral may increase their changes of operative death.
Adult↗
Influence of negative affect on smoking cessation treatment outcome: a pilot study.
In order to determine whether baseline depression was related to initial success or failure in smoking cessation, we prospectively examined mood self-ratings in a pilot study of 43 unselected smokers attempting to quit smoking in an outpatient program. Mean pretreatment POMS depression scores in the subjects who were unable to quit were significantly higher compared to those successful in initially relinquishing smoking. These preliminary results suggest that a negative-affect group at high risk for failure in nicotine dependence treatment might be identified in advance by an assessment of mood done prior to treatment.
Adult↗
Thermal coronary angiography: a method for assessing graft patency and coronary anatomy in coronary bypass surgery.
Thermal coronary angiography was evaluated in 50 patients undergoing 137 saphenous vein and 48 internal mammary artery bypass grafts. A total of 177 thermal coronary angiograms were performed after completion of the distal anastomoses by injection of cold cardioplegia into the vein or by reperfusion with warmer blood in the internal mammary artery grafts. These angiograms provided details of graft and anastomosis patency, flow directions, and presence of native coronary stenoses. Temperature differences between the injectant and the epimyocardium of greater than 4 degrees C resulted in high-contrast images. Thermal coronary angiograms were obtained in 173 of the 177 studied bypass grafts; 172 grafts were patent, and 1 internal mammary artery graft was occluded. Unsuspected stenoses were detected at the site of four distal anastomoses. Subsequently, two anastomoses were successfully revised and three additional grafts performed. Ninety-six native coronary stenoses were located in the recipient coronary arteries. In ten instances, the thermal coronary angiograms were obscured by excess fat or myocardium, thereby impeding correct image analysis. We conclude that thermal coronary angiography can be clinically relevant and helps improve decision making during coronary artery bypass operations.
Adult↗
[Digital thermo-coronary angiography--development and validation of the method in comparison with conventional cine-coronary angiography].
We describe the technique-thermal coronary angiography (TCA)-for real-time assessment of coronary anatomy and flow. The goal of this study was to compare thermal coronary angiography to cine coronary angiography and to validate its value for detecting stenoses. We studied the exposed LAD both in beating and arrested hearts in 11 open-chest pigs by TCA and cine angiography. We used an AGA 782 Thermovision system combined with a TIC 8000 digital image processor providing coronary images with 0.1-0.2 mm spatial and 0.1 degrees C thermal resolution, and a CFR x-ray system. The coronary arteries were catheterized via the right carotid artery, using standard 5F catheters. The thermal camera was focused at a 1m-distance to the heart surface and the x-ray was angled to LAO position. We performed simultaneous thermal and cine angiography using Angiovist 370 at different temperatures (10-40 degrees C) and injection rates (1-2.5 ml/s). Different grades of stenoses were created by snares. Thermistor probe readings of the epimyocardium and the left atrial blood were performed to reference the thermal camera measurements. We obtained high resolution TCA images of both the coronaries and of the myocardial perfusion beds whenever there was greater than 4 degrees C difference between injectate and epicardial temperature. The TCA detection of stenoses as compared to cine angiography was 29/30 (96.6%) in arrested and 36/42 (85.7%) in beating hearts. Coronary occlusion produced immediate and dramatic perfusion defects as detected by TCA. TCAs were highly reproducible. Injection rate of 2 ml/s provided optimal thermal coronary images. Thermal angiograms of the LAD were sometimes affected by large crossing coronary veins, myocardial bridges, and excess of fat pretending nonexistent coronary stenosis. TCA is a highly sensitive and reproducible method as compared to standard coronary angiography and allows for detection of coronary stenoses. The image quality was best in arrested hearts.
Animals↗
Use of the valvular resistance in the separation of normal and stenotic Hancock mitral valves.
Recent data suggests that the pressure-flow relationship for normal bioprosthetic mitral valves is linear. If this is correct, the valve resistance may provide a better indicator of normal mitral function than the Gorlin valve area. We compared the Gorlin valve area to the valve resistance (calculated as flow/pressure) in order to determine which better separated normal and stenotic Hancock mitral valves. Measurements were made using left atrial and left ventricular catheters in 42 patients undergoing Hancock mitral valve replacement. Patients were studied during pacing and isoproterenol infusion for a total of 141 measurements. Stenotic Hancock mitral valve hemodynamics were obtained at cardiac catheterization from eight patients who were studied at rest and during atrial pacing and from an additional eight patients culled from the literature (a total of 23 stenotic measurements). The Gorlin valve area ranged from 1.1 to 4.4 cm2 for the normally functioning Hancock valves and from 0.4 to 1.54 cm2 for the stenotic valves. Six measurements in patients with confirmed stenotic valves yielded Gorlin areas larger than the lowest area found in the normal valves and no value of the Gorlin valve area correctly classified all of the normal and the stenotic valves.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac Catheterization↗
Coronary angioscopy in patients with unstable angina pectoris.
To visualize intracoronary lesions in patients with different clinical expressions of coronary disease, we performed coronary angioscopy during coronary-artery bypass surgery in 10 patients with unstable angina and 10 patients with stable coronary disease. We examined a total of 32 vessels, using flexible fiberoptic angioscopes. Twenty-two vessels had no acute intimal lesion; three had complex plaques, six had thrombi, and one had both. Coronary angiography correctly identified the absence of complex plaque and thrombus in 22 vessels, but it detected only one of four complex plaques and one of seven thrombi. On angioscopy, none of the 17 arteries in the patients with stable coronary disease had either a complex plaque or thrombus. In the "offending" arteries of the patients with unstable angina, all three patients with accelerated angina had complex plaques and all seven with angina at rest had thrombi. We conclude that angioscopy frequently reveals complex plaques or thrombi not detected by coronary angiography. Our observations suggest that anginal syndromes that are refractory to medical treatment can be caused by unstable pathologic processes in the intima. Ulceration of plaques may increase the frequency and severity of effort angina, and the subsequent development of partially occlusive thrombi may cause unstable rest angina.
Adult↗
Aortic pseudo-aneurysm with Aspergillus aortitis. An unusual complication of coronary bypass surgery.
This is the first report of fatal postoperative Aspergillus infection in an aortic pseudoaneurysm associated with a jet lesion produced by a deformed, but hemodynamically normal aortic valve. Widespread arterial embolization was the principal feature and resulted in death on the 12th hospital day due to massive thromboembolism to the brain three months after successful coronary bypass surgery. Possible sources of such infections and the potential effect of the jet lesion are discussed.
Aged↗
Intraoperative coronary angioscopy. Technique and results in the initial 58 patients.
Coronary angioscopy provides images of intravascular detail with greater than 0.2 mm spatial resolution and excellent contrast resolution. Using endoscopes of 1.25 to 1.8 mm outer diameter, we performed intraoperative angioscopy of the coronary arteries or saphenous vein grafts, or both, in 58 patients. Eighty-one native coronary arteries and 43 vein grafts were examined. A clear viewing field was created by infusion of crystalloid cardioplegic solution through the aortic root during cardiopulmonary bypass. Technical details crucial for obtaining high-quality images were as follows: sufficient coronary perfusion by cardioplegic solution to displace all blood; adequate intraluminal illumination; and high-quality fiberoptic and lens systems. Incomplete studies in approximately 14% of patients were related to failure to achieve these technical details and lack of scope steerability. In 30% of patients, previously unrecognized anatomic details were revealed by angioscopy. These included intimal flaps at the site of vein-to-artery anastomoses, atheromatous plaques with adherent thrombi, and hemorrhagic ulcerated plaques, not recognized on angiography. Although a coronary intimal flap developed proximal to the anastomosis during retrograde examination in two patients, no serious complications occurred as a result of the procedure. We conclude that intraoperative angioscopy is safe, provides novel information that may be clinically relevant, and has future potential for development of the techniques for coronary endarterectomy and intraoperative balloon and laser angioplasty.
Angina, Unstable↗