Omega-3 fatty acids enhance tumor necrosis factor-alpha levels in heart transplant recipients.

BACKGROUND: Proinflammatory cytokines may contribute to clinical complications in heart transplant (HTx) recipients. Previous studies have shown immunomodulating effects of omega-3 fatty acids, but the results are somewhat conflicting. In this study, we examined plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 10, and their relations to antioxidant vitamins in 45 HTx recipients before and after treatment with omega-3 fatty acids or placebo. METHODS: The patients were long-time survivors of heart transplantation, randomized in a double-blind fashion to receive omega-3 fatty acids (3.4 g/day) or placebo for 1 year. Plasma levels of cytokines were measured by enzyme immunoassays and vitamin A, vitamin E, and beta-carotene by high-performance liquid chromatography. RESULTS: In the omega-3, but not in the placebo group, there was a rise in the proinflammatory cytokine TNF-alpha (P<0.05), a decrease in the anti-inflammatory cytokine IL-10 (P=0.07), and a rise in TNF/IL-10 ratio (P<0.05) after 12 months, suggesting a proinflammatory net effect. In the omega-3 group, the increase in TNF-alpha was associated with an increase in eicosapentaenoic acid in plasma (r=0.58, P<0.02). During omega-3 fatty-acid treatment, but not during placebo, there was a decrease in vitamin E (P<0.05) and beta-carotene (P<0.05) levels, and the decrease in vitamin E was inversely correlated with the increase in TNF-alpha (r= -0.56, P<0.01). The rise in TNF-alpha levels during omega-3 fatty acids treatment was most pronounced in those patients with transplant coronary artery disease (P<0.04). CONCLUSION: Our data suggest that omega-3 fatty acids in HTx recipients may change the balance between proinflammatory and anti-inflammatory cytokines in an inflammatory direction, possibly related to prooxidative effects of these fatty acids.     

Effects of omega-3 fatty acids on acute necrotizing pancreatitis in rats

The aim of this study was to investigate the influence of omega-3 fatty acids (omega3FA) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increases in mortality rate, intestinal permeability, bacterial infection in pancreas and extrapancreatic organs, and serum activity of urea and amylase, alanine transferase (ALT), interleukin (IL)-6, tumor necrotizing factor-alpha (TNF-alpha), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and a considerable decrease of concentrations of calcium, protein and albumin. The use of omega3FA reduced mortality, phenol sulfophthalein excretion in urine, bacterial infection in pancreas, liver, spleen, MPO and MDA levels in pancreatic and lung tissue, LDH level in BAL fluid and serum IL-6 and TNF-alpha values. Serum triglyceride increased only in the omega3FA groups. Serum amylase, ALT, calcium, urea, protein, IL-1, and degree of pancreatic damage indicated no difference between the pancreatitis groups. Increased intestinal permeability and cytokine levels, and free radical damage play an important role during the course of acute pancreatitis. The treatment with omega3FA improves these effects. omega3FA may be useful in the treatment during ANP in rats. Therefore, it can be beneficial in patients with pancreatitis.     

Pulmonary complications in heart transplant recipients

BACKGROUND: Heart transplantation is an important therapeutic option for patients with end-stage disease, but is associated with major pulmonary complications. PATIENTS AND METHODS: We retrospectively reviewed the posttransplant follow-up of 34 orthotopic heart transplant recipients. RESULTS: Two of the 34 patients died of cardiac failure in the early postoperative period. Among the surviving patients, 10 (31.3%) developed pulmonary complications, all within the first 6 months: hospital-acquired bacterial pneumonia in five, fungal pneumonia in three, posttransplant lymphoproliferative disease in one, and community-acquired pneumonia in one patient. None of the patients developed transplantation-related malignancy. The overall mortality was 35.3%. Pneumonia-related mortality rate of 14.7% was due to early-onset nosocomial pneumonias, which were caused by bacterial and opportunistic microorganisms. Extrapulmonary causes of mortality were cardiac failure, meningitis, septicemia, and acute rejection. Cytomegalovirus antigenemia in the first month was associated with a poor prognosis. The frequency of pulmonary complications was higher among older patients and those who developed moderate rejection in the first month (P=.014 and P=.036, respectively). CONCLUSION: Pulmonary infections after heart transplantation occurred more frequently during the first 6 months posttransplantation, accounting for a significant portion of the posttransplantation mortality.     

Gallstone disease in heart transplant recipients

OBJECTIVE: To review the outcome of cholecystectomy after heart transplant. SUMMARY BACKGROUND DATA: The optimal timing for gallbladder surgery in heart transplant patients is controversial. METHODS: Between April 1985 and October 2000, 518 cardiac transplants were performed at Ochsner Foundation Hospital. Data gathered included ultrasound reports, cholecystectomy operative reports, gallbladder pathologic reports, complications, and deaths. RESULTS: Charts were available for 509 patients (98%), 68 (13%) of whom underwent cholecystectomy before transplantation. Of the 509, 53 (10%) had serial ultrasound examinations and 29 of the 53 (55%) developed gallstones. After transplant, 47 (9%) underwent cholecystectomy. Five cholecystectomies were performed during the immediate postoperative course. Two patients who underwent cholecystectomy had acalculous cholecystitis; one was incidental. Four patients died (one with rejection and three with sepsis). After discharge, 42 cholecystectomies were performed: 16 for biliary colic (no deaths, three patients with complications), 19 for acute cholecystitis (one death, nine patients with complications), 5 for biliary pancreatitis (1 death, 1 patient with complications), and 2 others. CONCLUSIONS: The risk of morbidity and mortality from gallstone disease is high in cardiac transplant patients, particularly immediately posttransplant. Posttransplant patients require annual ultrasound examinations to detect the onset of gallstone disease, and this risk is higher than in the general population. Gallstones alone are an indication for cholecystectomy in the cardiac transplant patient. Pretransplant cholecystectomy should be considered in clinically stable patients with gallstones.     

Acute diverticulitis in heart transplant recipients

Immunosuppressed patients are susceptible to complicated diverticulitis, but reports of this complication are scarce in heart graft recipients. To estimate the prevalence of acute diverticulitis in heart graft recipients, we retrospectively reviewed the cases of diverticulitis in a series of 143 patients who underwent orthotopic heart transplantation in a period of 10 years. Six (4%) of these developed acute diverticulitis and required colectomy. All of them were male patients and were older than 50 years. Four patients underwent urgent laparotomy and colon resection with end colostomy (Hartmann procedure). The two other patients suffered from diverticulitis without generalized peritonitis and underwent laparoscopic sigmoidectomy with direct transanal end-to-end anastomosis. The postoperative outcomes of these six patients were satisfactory. As are other immunosuppressed patients, heart graft recipients are susceptible to diverticulitis. Early surgical management may be safe in well-compensated patients.     

Aortic aneurysm in heart transplant recipients

Purpose: The purpose of this study was to define the clinical features of aortic aneurysms occurring in heart transplant recipients.Methods: Among the 734 patients who have undergone heart transplantation at our institution over the last 14 years, we have identified 12 patients (1.6% incidence) with aortic aneurysms (9 infrarenal, 3 thoracoabdominal), making this the largest reported series of aortic aneurysms (AA) in heart transplant recipients.Results: For nine of the 12 patients with AA (75%), the indication for transplantation was ischemic cardiomyopathy. This indication accounted for only 42% of the overall transplantation group; our data therefore show that the risk of infrarenal AA disease was higher for patients who underwent transplantation for ischemic cardiomyopathy than for other indications ( p = 0.02). In two of the patients with thoracoabdominal AA, chronic dissection was identified as the specific AA cause, whereas all of the other patients in the study had nonspecific "atherosclerotic" AAs. All 12 patients were symptom free at the time of initial discovery of the AAs. Two of the patients with infrarenal AA were diagnosed with AAs before transplantation; for the seven remaining patients with infrarenal AAs, the mean time between transplantation and AA discovery was 5.0 years (range 1.2 to 11.8 years). Serial radiologic studies allowed us to determine the AA expansion rate in seven of the 12 patients. This rate varied from 0 to 2.53 cm/yr (mean 1.20 cm/yr; 1.0 cm/yr for infrarenal AA alone). Five patients with infrarenal AA underwent AA repair as the initial treatment. Three others underwent repair after their AAs significantly expanded under observation. Mean AA diameter at the time of repair was 6.9 cm. All three patients with thoracoabdominal AAs died of acute AA rupture before resection could be done, despite their initial asymptomatic state. AA diameters at time of rupture were 3.5, 6.0, and 11 cm. All of the eight patients with AA treated with surgery are alive and well (median follow-up 18 months). The only complication was acute heart transplant rejection, which occurred 11 days after AA repair in one patient.Conclusions: Our data suggest that AA occurrence is more likely in patients who undergo heart transplantation for ischemic heart disease than for other indications. Careful serial radiologic surveillance is warranted in any heart transplant patient with an AA, because of the apparent potential for more rapid AA expansion in this patient population than in patients who do not undergo transplantation. We conclude that early repair of infrarenal AA is indicated because excellent operative results and low morbidity rates can be achieved. An aggressive approach to thoracoabdominal AAs in this group may also be appropriate because of the apparent propensity to lethal rupture, sometimes at relatively small AA size. (J VASC SURG 1995;22:689-96.)     

Platelet activation in heart transplant recipients

An inappropriate and persistent immune activation has been suggested to contribute to long-term mortality and morbidity after heart transplantation. Several lines of evidence suggest that platelets do not only promote thrombus formation, but also act as inflammatory cells. In the present study, we investigated if long-time survivors of heart transplantation (mean time since transplantation 6.5 yr) were characterized by enhanced platelet activation as assessed by different experimental approaches. Our main findings when comparing heart transplant recipients (n = 52) and age- and sex-matched healthy controls (n = 38) were: (i) platelets from heart transplant recipients showed enhanced expression of both P-selectin and CD63 as assessed by flow cytometry; (ii) platelets from these patients also contained significantly increased levels of soluble CD40 ligand and tended to release higher levels of this cytokine upon SFLLRN stimulation as assessed by enzyme immunoassay; (iii) heart transplant recipients had increased levels of soluble P-selectin in platelet-free plasma; and (iv) the enhanced platelet activation after heart transplantation was most pronounced in those with concomitant hypertension. These findings suggest that long-term survivors of heart transplantation are characterized by enhanced activation of platelets, possibly contributing to the persistent immune activation and clinical complications in these patients.     

omega-3 fatty acids decrease endothelial adhesion of human colorectal carcinoma cells

BACKGROUND: Diets rich in omega-3 fatty acids have been shown to decrease both the initiation and promotion of colon carcinogenesis although their effect on hepatic metastasis formation is less well understood. Since adhesion of human colorectal carcinoma (HCRC) cells to hepatic endothelial cells is an important step in the metastatic cascade, the effect of membrane omega-3 fatty acid alterations on endothelial cell adhesion was studied. MATERIALS AND METHODS: CX-1 cells, a moderately differentiated HCRC cell line known to produce hepatic metastases in an athymic mouse intrasplenic injection model, were used. Cells were grown in omega-3 fatty acid-enriched medium and membrane-free fatty acid modifications confirmed with gas chromatography. Both human umbilical vein and hepatic sinusoidal endothelial cells were used in the binding assays. Adhesion assays were performed in a standard fashion using (51)Cr-labeled cells to tumor necrosis factor (TNF)-stimulated endothelial cell monolayers. Immunohistochemical analysis was performed for sialyl-Lewis(x), the receptor involved in endothelial adhesion on the surface of control and fatty acid-modified cells. RESULTS: Gas chromatographic analysis confirmed membrane fatty acid modification of CX-1 cells by growth in docosahexanoic acid (omega-3) (4.761 nmol/10(6) cells vs 0.057 nmol/10(6) cells for controls). Binding of CX-1 to both human umbilical vein and hepatic sinusoidal endothelial cells decreased from 38.4 +/- 0.44 to 11.58 +/- 0.87% (P < 0.01). Immunocytochemical analysis showed a decrease in sialyl-Lewis(x) expression with omega-3 treatment. CONCLUSIONS: These data indicate that omega-3 fatty acids may also be protective against the formation of hepatic metastases. The mechanism for this may be decreased endothelial cell adhesion which in turn may be due to decreased expression of the endothelial receptor sialyl-Lewis(x).     

Pregnancy in heart transplant recipients.

The aim of this report is to present data from Italian cardiac transplant centers assessing pregnancy after cardiac transplantation. Our retrospective survey included 10 pregnancies occurring in 7 patients during January 1991 to February 2002. Eight pregnancies were completed successfully and 2 abortions were reported (frequency rate 20%). No complications were observed during pregnancy or after delivery. Of 8 infants studied, 6 (75%) were born at term and 2 (25%) pre-term. One baby presented congenital talipes valgus. Pediatric development was uneventful. The data from the literature and our series show that a multidisciplinary approach is mandatory. The course of pregnancy is usually normal and the maternal and fetal outcomes are usually favorable. Although no fetal malformations have been reported, prolonged follow-up of these infants is required.     

Plasma adiponectin in heart transplant recipients

Abstract: Background: The association between plasma adiponectin and metabolic syndrome may be impaired in heart transplant recipients, since renal failure is frequent among these patients. Thus, we studied the relationship between metabolic syndrome and plasma adiponectin in transplanted heart recipients. Methods: Ninety‐five heart transplant recipients were prospectively included 8.3 ± 5.6 yr after transplantation in this cross‐sectional study. All patients had physical examination, echocardiography or routine biennial coronary angiography, and laboratory measurements. Results: Metabolic syndrome was found in 31% of these patients. Plasma adiponectin was significantly lower in patients with metabolic syndrome (12.5 ± 8.3 μg/mL) than in patients without (16.7 ± 9.4 μg/mL, p = 0.03). Adiponectin levels were usually in the normal or high range (< 4 μg/mL in only two patients). Low creatinine clearance was associated with higher plasma adiponectin (R=?0.26, p = 0.01). Plasma adiponectin was not significantly different between the 28 patients with angiographic evidence of graft vasculopathy (13.9 ± 9.5 μg/mL) and the 67 patients without (16.1 ± 9.1 μg/mL, p = 0.3). Conclusions: Contrasting with a high frequency of metabolic syndrome in these patients, adiponectin levels were usually in the normal or high range, probably as a consequence of renal failure. This suggests that adiponectin is not a major determinant for insulin resistance among these patients.     

心脏移植受者居家自我管理体验的质性研究

目的了解心脏移植受者居家自我管理体验及需求。方法对13例心脏移植受者进行半结构式访谈了解其居家自我管理的体验,采用Colaizzi现象学研究法分析资料。结果心脏移植受者居家自我管理体验可归纳为4个主题:复杂的内心世界、自我管理需要不断学习、居家自我管理的困惑、自我管理的压力与动力。结论了解心脏移植受者居家自我管理存在一定的困惑与问题,护理人员需提供个性化护理方案、建立有效的社会支持,以提高心脏移植受者的居家自我管理能力。     

Pathologic assessment of cardiomyocytes in heart transplant recipients treated with rapamycin or cyclosporine

The aim of this study was to compare cardiomyocytes and stromal pathology in heart transplant recipients treated with rapamycin (RAPA) versus cyclosporine (CyA). We analyzed elective biopsies obtained during first 3 months after heart transplantation in four patients treated with RAPA (24 biopsies) and seven patients receiving CyA (49 biopsies). Additional medications in both groups consisted of mycophenolate mofetil or azathioprine and prednisone. The intensity of rejection was assessed using the ISHLT scale; it was comparable in both groups based upon the number of results showing significant rejection and the average biopsy scores. Each slide was also examined under high-power magnification to sarcoplasmic and nuclear changes. Sarcoplasmic vacuolation, premyocytolysis and myocytolysis, nuclear staining, stromal fibrosis and edema, presence of vasculopathy, and lymphocytes infiltrating the myocardium occurred more frequently in the CyA group. The difference in the degree of hyperchromasia of the nuclei was highly significant (67% versus 10%, P <.00001). Our findings suggest that despite comparable levels of rejection as assessed using the ISHLT scale, patients treated with RAPA display fewer signs of cardiomyocytic alterations early after heart transplantation.