Porous plug gas injection systems for studies of hydrocarbon dissociation and transport in the DIII-D tokamak.

A probe has been designed, constructed, and successfully used to inject methane into the DIII-D lower divertor in a manner imitating natural release by chemical erosion. This porous plug injector (PPI) probe consists of a self-contained gas reservoir with an integrated pressure gauge and a 3 cm diameter porous surface through which gas is injected into the lower divertor of the tokamak. The probe is positioned flush with the divertor target surface by means of the divertor materials evaluation system. Two gas delivery systems were developed: in the first, gas flow is regulated by a remotely controlled microvalve and in the second by a fixed micro-orifice flow restrictor. Because of the large area of the porous surface through which gas is admitted, the injected hydrocarbon molecules see a local carbon surface (>90% carbon) similar to that seen by hydrocarbons being emitted by chemical sputtering from surrounding carbon tiles. The distributed gas source also reduces the disturbance to the local plasma while providing sufficient signal for spectroscopic detection. In situ spectroscopic measurements with the PPI in DIII-D allow the direct calibration of response for measured plasma conditions from a known influx of gas.

Rare case of heart failure caused by compression of the left atrium by a thoracic aortic aneurysm.

A 61 year old patient was found to have an aneurysm extending from the aortic root to the suprarenal region. He underwent first stage surgery with aortic root and arch replacement, prosthetic aortic valve replacement, and coronary artery bypass grafting. Four weeks later, he presented with breathlessness and signs of heart failure and pleural effusion. Computed tomography showed that the left atrium was compressed between the aortic aneurysm posteriorly and the left ventricle and sternum anteriorly. Obstruction of the superior vena cava, bronchus, oesophagus, and rarely right atrium by an aortic aneurysm has been described before but presentation with left atrial compression has not been reported.

Tumour necrosis factor alpha gene polymorphism: a predisposing factor to non-ischaemic myocardial dysfunction?

BACKGROUND: Tumour necrosis factor alpha (TNF alpha) is implicated in the pathophysiology of heart failure. Plasma TNF alpha is raised in patients with myocardial dysfunction in proportion to the symptoms. OBJECTIVE: To determine whether this genetic variant is over represented in heart transplant recipients. PATIENTS: 175 heart transplant recipients and a control group of 212 healthy volunteers were studied. The reason for transplantation was severe symptomatic myocardial dysfunction in all cases. METHODS: The TNF alpha genotype was determined by polymerase chain reaction and gel electrophoresis. The populations were compared for their fit to Hardy-Weinberg equilibrium by calculating the expected frequencies of each genotype and comparing them to the observed values. A chi(2) test was used to determine the significance of the difference between the observed and expected values. RESULTS: No differences were found in the frequency of the TNF2 allele between all heart transplant recipients taken together (54/175, 31%) and healthy volunteers (58/212, 27%). A higher proportion of TNF2 allele carriers was present in cardiac recipients with a pretransplant diagnosis of viral mediated or idiopathic heart failure than in those with ischaemic myocardial dysfunction (26/69 (37.7%) v 28/106 (26.4%), p = 0.03). PATIENTS with a non-ischaemic aetiology had a higher prevalence of TNF2 than healthy volunteers (26/69 (37.7%) v 58/212 (27%), p = 0.05). CONCLUSIONS: The TNF2 allele is overrepresented in patients with end stage non-ischaemic myocardial dysfunction. This may represent a genetic predisposition in a small subset of patients who could respond favourably to anti-TNF alpha treatment.

Influence of tumor necrosis factor-alpha gene-308 polymorphism on the development of coronary vasculopathy after cardiac transplantation.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been implicated in cardiovascular disease. Polymorphism of the TNF-alpha gene promoter region (position -308) influences an individual's production of TNF-alpha. This affects susceptibility to acute rejection after cardiac transplantation. Because the highest serum levels of TNF-alpha have been found in recipients with cardiac transplant vasculopathy and because TNF-alpha blockade can prevent the disease in rabbits, we investigated the effect of TNF-alpha promoter polymorphism on the development of vasculopathy in human cardiac allograft recipients. METHODS: Using sequence-specific primers to the TNF-alpha gene and polymerase chain reaction, the genotypes of 147 cardiac transplant recipients and 134 heart donors were identified. An association was sought between the presence of high-producing (A homozygotes, GA heterozygotes) or low-producing (G homozygotes) TNF-alpha genotype and the development of coronary vasculopathy, diagnosed by routine surveillance coronary angiography. RESULTS: We found that 31.9% of recipients and 27.0% of donors were high TNF-alpha producers. The presence of the high-producing TNF-alpha allele led to an earlier diagnosis of vasculopathy; 3.42 years (+/- 91.3 days) vs 3.84 years (+/- 76.3 days) for high- and low-producing cardiac graft recipients, respectively; 3.52 years (+/- 87.3 days) vs 3.78 years (+/- 77.4 days) for high- and low-producing donor grafts, respectively. However, neither of these differences were significant. By Kaplan Meier actuarial analysis and log-rank test, TNF-alpha polymorphism had no effect on the freedom from vasculopathy when considering either recipient (p = 0.99) or donor (p = 0.86) TNF-alpha genotype. Multivariate analysis identified increasing donor age and the number of acute rejection episodes of International Society for Heart and Lung Transplantation grade 3 or greater as independent risk factors for vasculopathy in both the recipient and donor cohorts. CONCLUSIONS: Polymorphism at position -308 in the promoter region of the TNF-alpha gene fails to predict the development of cardiac transplant-related vasculopathy and cannot be used as a genetic risk marker. This may be because of the effects of immunosuppressive treatment.

Impact of stenting on coronary angioplasty procedures.

OBJECTIVE: To compare patient selection and outcome of coronary angioplasty procedures before and after the widespread availability and use of stents. SUBJECTS AND METHODS: Group 1 consisted of 252 consecutive patients and group 2 comprised 389 patients who underwent angioplasty between April 1993 and March 1994, and April 1995 and March 1996, respectively, in a tertiary cardiothoracic centre. Clinical variables were collected before the procedures. Endpoints included in-hospital death, the need for repeat coronary angiography, repeat angioplasty, and coronary artery bypass surgery. Lesions were classified under American Heart Association/American College of Cardiology criteria in 100 randomly selected patients from each group. RESULTS: 311 and 482 angioplasty procedures were performed in patients from groups 1 and 2, respectively. One or more stents were deployed in nine (4%) and 179 (46%, p < 0.01) patients, respectively. The success rate was higher in group 2 than in group 1 patients (483/523 (92%) v 274/372 (88%), respectively, p < 0.05). There were significantly more single vessel angioplasty procedures (198/252 (79%) v 272/389 (70%), p < 0.05), type A lesions (30/116 (26%) v 19/130 (15%), p < 0.05), patients with stable angina (220/252 (87%) v 311/389 (80%), p < 0.05), and fewer acute myocardial infarction patients (1/252 (0%) v 12/389 (3%), p < 0.05) treated in group 1 than in group 2, respectively. Similar numbers of angioplasty were performed in the left anterior descending, left circumflex, and right coronary arteries. There were no significant differences in the in-hospital mortality or the need for repeat coronary angiography, angioplasty, or bypass surgery at 24 hours or six months after the initial procedure. CONCLUSION: Patients undergoing angioplasty in the stenting era had features associated with an increased risk of complication. Despite this, the primary success rate was higher, and the complication rate and the need for subsequent revascularisation were similar in the two groups, supporting the widely held clinical impression that stenting has made a valuable impact on the practice of angioplasty.

Expression of cytokine messenger RNA after heart transplantation: relationship with rejection and serum cytokines.

Different groups of cytokines may initiate or inhibit the rejection process. We used the polymerase chain reaction to study the expression of cytokine mRNA for interleukin (IL)-2, -4, -6 and -10, tumor necrosis factor-alpha, and interferon-gamma in 187 biopsy specimens from 24 human cardiac transplant recipients 5-555 days after transplantation. Cytokine levels in the serum were also measured. Cytokine mRNA was detected in 38.5% of biopsy specimens. IL-10 mRNA was detected more frequently with mild or absent rejection (11.6% in grades 0 and 1 - vs. 1.4% in grades 2 and 3, P=0.01). Up to 90 days after transplantation, IL-2 mRNA was detected more frequently with moderate rejection (13% in grades 2 and 3 vs. 0% in grades 0 and 1, P=0.076), and IL-4 mRNA was detected more frequently with mild or absent rejection (16% in grades 0 and 1 - vs. 0% in grades 2 and 3, P=0.061). More than 90 days after transplantation, IL-2 mRNA was detected more frequently with mild or absent rejection (10% in grades 0 and 1 vs. 0% in grades 2 and 3, P=0.078). Serum IL-4 levels corresponding to biopsy specimens positive for IL-4 mRNA were higher than those corresponding to specimens negative for IL-4 mRNA (59 pg/ml vs. 32 pg/ml medians, P=0.028). Our results suggest that IL-10 and possibly IL-4 (T helper 2 cytokines) may suppress graft rejection, whereas IL-2 (T helper 1 cytokine) may promote cellular rejection. In addition, cytokine profiles may change with length of time after transplantation. The association of elevated serum levels of IL-4 with increased expression of intragraft IL-4 mRNA may suggest release of this cytokine from the graft into the circulation.

Serum cytokines in human heart transplant recipients. Is there a relationship to rejection?

Cytokines are important in the pathogenesis of allograft rejection. Some studies have suggested a positive relationship between serum levels of cytokines and rejection, so this study was designed to investigate the presence of a range of cytokines in a large cohort of cardiac transplant recipients. We used enzyme linked immunosorbent assays (ELISA) to examine sequential serum samples from 28 consecutive heart transplant recipients; length of follow up varied between 2 and 566 days (median 357 days). Serum levels of IL-2, 4, 6, 10, TNF-alpha, and IFN-gamma were measured. We compared these results with detailed data on patients' clinical courses, including histological rejection, infection, and therapeutic use of antithymocyte globulin (ATG). No significant relationship was found between rejection and serum cytokine levels for samples taken more than 30 days after transplantation. Prior to this cytokine levels were significantly disturbed by the use of cytolytic therapy for induction immunosuppression. Serum cytokine levels sometimes showed peaks that appeared to be related to rejection, or occasionally to infection, but these relationships were not consistent. Serum TNF-alpha and IL-6 were consistently elevated within a few days of administration of ATG. We conclude that there is no systematic relationship between serum cytokine levels and histological rejection or infection in cardiac transplant recipients.

Management of heart failure. II. Counseling, education, and lifestyle modifications.

OBJECTIVE: This article reviews the role of counseling, education, dietary modifications, and exercise for patients with heart failure due to left ventricular systolic dysfunction. DATA SOURCE: We reviewed studies published in English between 1966 and 1993 and referenced in MEDLINE or EMBASE. We used the search terms heart failure, congestive; congestive heart failure; heart failure; cardiac failure; and dilated cardiomyopathy in conjunction with terms for the specific areas of interest. Where data were lacking, we relied on opinions of panel members and peer reviewers. STUDY SELECTION AND DATA SYNTHESIS: Studies were reviewed to determine whether patients had heart failure due to systolic dysfunction (left ventricular ejection fraction, < 0.35 to 0.40) and whether clinical outcomes were reported. Studies that reported only intermediate outcomes (eg, hemodynamics) were not reviewed. CONCLUSION: Counseling and education can improve patient outcomes and decrease unnecessary hospitalizations. Patients with mild to moderate heart failure should be restricted to 3 g/d of sodium initially. Those who are unresponsive to this dosage or who have more severe disease should be advised to consume 2 g/d or less. Patients should be strongly advised to drink no more than 30 mL/d of alcohol or, preferably, to abstain completely. Exercise training is safe and can improve exercise duration and symptoms. Adherence to the treatment plan should be stressed and monitored at each visit. Clinicians should inform patients of the seriousness of their disease and their prognosis, but they should emphasize that patients can continue to remain active and enjoy a reasonable quality of life.

Wegener's granulomatosis and the heart.

Three cases of Wegener's granulomatosis with cardiac complications are described and the relevant published reports are reviewed. The first case of Wegener's granulomatosis was associated with aortic regurgitation and required aortic valve replacement. The second and third cases were associated with pericardial disease requiring pericardiectomy for constructive pericarditis in one case, and haemorrhagic pericarditis with pericardial effusion in the other. Aortic valve involvement in Wegener's granulomatosis is uncommon and valve replacement has been described on only one previous occasion. Pericardial involvement is relatively common pathologically, but pericardial surgery has been described in this condition only twice, once for tamponade and once for constrictive pericarditis after pericardiocentesis. Cardiac involvement is not uncommon in patients with Wegner's granulomatosis and may be clinically important. Diagnosis is aided by estimation of the anti-neutophil cytoplasmic antibody titre.

Failure of balloon dilatation of the pulmonary valve in carcinoid pulmonary stenosis.

BACKGROUND: Carcinoid heart disease typically results in pulmonary stenosis and tricuspid incompetence. Percutaneous balloon dilatation is an effective treatment for congenital pulmonary stenosis and has been applied successfully to tricuspid stenosis caused by carcinoid heart disease. The value of balloon dilatation of the pulmonary valve in carcinoid pulmonary stenosis was assessed. METHODS: Two patients with severe congestive heart failure secondary to carcinoid heart disease and with documented pulmonary stenosis had balloon dilatation of the pulmonary valve. In both cases tricuspid regurgitation was also present together with reduced cardiac output. RESULTS: The procedure was technically successful in both patients. One patient experienced symptomatic benefit for two months and the other experienced no improvement. Both patients subsequently required combined tricuspid and pulmonary valve replacement from which good results and symptomatic improvement were obtained. CONCLUSION: Though balloon dilatation of the pulmonary valve is technically feasible it is unlikely to provide useful palliation in carcinoid heart disease. Valve surgery should be considered in patients in whom the malignancy is controlled but carcinoid heart disease is producing drug resistant congestive heart failure.

Desirability of immediate surgical standby for coronary angioplasty.

OBJECTIVE: To assess the value of emergency surgical standby for percutaneous transluminal coronary angioplasty. DESIGN: Retrospective review of the major complications of coronary angioplasty in a regional cardiac centre. SETTING: All angioplasties were performed in the cardiac catheterisation laboratory of Wythenshawe Hospital with surgical standby in an adjoining operating theatre. PATIENTS: 1262 vessels were dilated in 1032 patients (mean age 53 years) between 1984 and 1989. MAIN OUTCOME MEASURES: In-hospital mortality from emergency surgical revascularisation after angioplasty; the rate of myocardial infarction and overall morbidity. RESULTS: Coronary angioplasty achieved primary success in 90% of cases. Thirty eight (3.7%) patients (five women (mean age 55.8) and 33 men (mean age 53.0] were referred for urgent surgical revascularisation--36 direct to operation and two within 24 hours. All patients survived surgery. Five of the 38 had had a previous angioplasty to the same vessel and one had had previous coronary artery grafts. Four of the 38 had an angioplasty for unstable angina. Eighteen had single, 13 double, and seven triple vessel coronary artery disease. The target vessel was the left anterior descending in 25, right coronary artery in nine, circumflex in three, and the left anterior descending and circumflex coronary arteries in one. Five required external cardiac massage on the way to the operating theatre; two of them had a left main stem occlusion. Four internal mammary artery and 60 reversed saphenous vein grafts were implanted (1.6 per patient). Complete revascularisation was achieved in 36 (94.7%) patients. Q wave myocardial infarction occurred in six (15.8%). The final outcome was: none dead, three patients with angina, one late death, one cerebrovascular accident, one late operation for a new left anterior descending lesion, two patients on diuretics with or without an angiotensin converting enzyme inhibitor. One orthotopic transplant was performed in a patient in whom cardiogenic shock developed after the left anterior descending coronary artery became occluded 72 hours after angioplasty. CONCLUSION: There was no surgical mortality and low morbidity among patients for whom immediate surgical cover was requested.

Aortic valve replacement with combined myocardial revascularisation.

Early and late outcome was studied in 630 patients who underwent aortic valve replacement between 1974 and 1982. Group 1 (506 patients) did not have important coronary artery disease, group 2 (69 patients) had coronary artery disease and underwent coronary artery bypass grafting, and group 3 (55 patients) had coronary artery disease but did not undergo myocardial revascularisation. Early mortality (within 30 days of operation) was significantly lower for group 1 (6%) than for group 2 (13%) and for group 3 (16%). Operative mortality in all three groups was lower in patients operated on more recently. The three year survival of patients in group 1 (83%) was significantly higher than that of patients in group 3 (62%) but not than that of patients in group 2 (76%). The findings of this study suggest that the presence of coronary artery disease increases the risk of aortic valve replacement whether or not coronary artery grafting is performed. Myocardial revascularisation, however, seems to return patients with aortic valve and coronary artery disease to a survival curve similar to that of patients with isolated aortic valve disease.

Actuarial analysis of late results after closed mitral valvotomy.

The long-term results of closed mitral valvotomy performed between 1978 and 1985 in 198 patients with noncalcific mitral stenosis were analyzed. Follow-up data were available on 185 patients (93%); 1 patient died in the postoperative period, and 12 foreign patients were lost to follow-up. At the 4-year and 8-year intervals, 91% and 80% of patients, respectively, were event free (not in need of further operative procedures). By multivariate analysis, the factor preoperative mild mitral regurgitation showed a tendency to influence the event-free period. By univariate analysis, postoperative mitral regurgitation significantly reduced the event-free period. Twenty-one patients subsequently underwent mitral valve replacement; 8 for mitral regurgitation, 10 for mitral stenosis, and 3 for mixed mitral regurgitation and stenosis. By multivariate analysis, the reason for reoperation significantly influenced the length of the event-free period. The patients with mitral regurgitation required mitral valve replacement sooner than those with mitral stenosis. Advanced age, sex, previous valvotomy, preoperative New York Heart Association Functional Class, low mitral valve leaflet excursion, and pulmonary hypertension had no influence on the long-term result.

Left ventricular dysfunction in patients with angina pectoris and normal coronary angiograms.

Left ventricular function was assessed in 201 patients who presented with angina pectoris and who were subsequently found to have completely normal coronary angiograms. Left ventricular angiograms from 187 patients were suitable for analysis of systolic regional wall motion; 121 were found to be normal and 66 had a total of 115 hypokinetic segments. Patients with hypokinesia had a significantly higher left ventricular end systolic volume and a significantly lower left ventricular ejection fraction and exercise capacity than those in whom regional wall motion was normal. Thirty one per cent of patients with normal wall motion and 30% of those with hypokinesia had a resting left ventricular end diastolic pressure greater than 15 mm Hg. There were significantly more smokers in the group with hypokinetic segments. Thus of patients with angina and normal coronary angiograms, 25% had evidence of left ventricular systolic dysfunction, 20% had evidence of diastolic dysfunction, and 11% had evidence of both systolic and diastolic dysfunction. The results suggest that smoking may be associated with left ventricular regional wall motion abnormalities.