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Biomedical subjects

Folke Nilsson

Publications and source records attributed to Folke Nilsson.

14 recordsLinked to original sources

Ex vivo evaluation of nonacceptable donor lungs.

BACKGROUND: Only a minority of the potential candidates for lung donation are considered suitable, using current evaluation methods. A new method for ex vivo evaluation, with the potential for reconditioning of marginal and nonacceptable lungs, has been developed. This is a report of the ex vivo evaluation of six donor lungs deemed nonacceptable (arterial oxygen pressure less than 40 kPa) by the Scandiatransplant, Eurotransplant, and UK transplant organizations. METHODS: The lungs are perfused ex vivo with Steen solution, a lung evaluation-preservation solution, mixed with red blood cells to a hematocrit of 15%. This extracellular solution is designed to have an optimal colloid osmotic pressure so that physiologic pressure and flow can be maintained without development of pulmonary edema. An oxygenator connected to the extracorporeal circuit maintains a normal mixed venous blood gas level in the perfusate. The lungs are ventilated and evaluated through analyses of pulmonary vascular resistance, oxygenation capacity, and arterial carbon dioxide pressure minus end-tidal carbon dioxide difference. RESULTS: The arterial oxygen pressure (inspired oxygen fraction, 1.0) increased from 27 kPa (range, 17 to 34 kPa) in situ in the organ donor at the referring hospital to 57 kPa (range, 39 to 66 kPa) during the ex vivo evaluation. The pulmonary vascular resistance varied from 3.2 to 5.7 Wood units, and the arterial carbon dioxide pressure minus end-tidal carbon dioxide difference was in the range of 1 to 2.5 kPa. CONCLUSIONS: The arterial oxygen pressure improves significantly in this model. This ex vivo evaluation model is a valuable addition to the armamentarium in finding acceptable lungs in a donor population with inferior arterial oxygen pressure values.

Carbon Dioxide↗

Vascular resistance and endothelial function in cyclosporine-treated lung transplant recipients.

The majority of patients undergoing solid organ transplantation develop hypertension, to which vasoconstriction and impaired endothelial function have been suggested to contribute. We compared basal vascular resistance and nitric oxide-mediated endothelial-dependent and independent vasoreactivity between cyclosporine-treated lung transplant recipients and healthy subjects. Forearm blood flow was measured by venous occlusion plethysmography at rest and during acetylcholine, glyceryltrinitrate and N(G)-monomethyl-L-arginine acetate (L-NMMA) infusion in 11 lung transplant recipients 3-5 years after transplantation and in eight healthy subjects. Forearm vascular resistance (FVR) was calculated. Plasma levels of endothelin-1 (ET-1) and von Willebrand factor (vWf) were analysed. Basal vascular resistance was 40% lower in transplant recipients than in healthy subjects (P = 0.021). Endothelial-dependent and independent vasodilation did not differ. Plasma levels of ET-1 and vWf were higher in transplant recipients (P = 0.009 and P < 0.001 respectively). There was a significant correlation between ET-1 levels and FVR in healthy subjects (r = 0.83, P = 0.042), but not in transplant recipients (r = -0.14, P = 0.70). The findings oppose the theory of generalized vasoconstriction and impaired endothelial function in the pathogenesis of hypertension after transplantation. Increased plasma levels of ET-1 do not cause increased FVR in lung transplant recipients.

Adult↗

Effect of lung volume reduction surgery for emphysema on diaphragm function.

Preoperative prediction of a successful outcome following lung volume reduction surgery (LVRS) for emphysema is imperfect. One mechanism could be improvement in respiratory muscle function yet controversy exists regarding the magnitude and mechanism of such an improvement. Therefore, we measured diaphragm strength in 18 patients before and after LVRS. Mean (S.D.) FRC fell from 6.53 to 5.40 l (p = 0.0001). Mean sniff transdiaphragmatic pressure increased from 76 to 87 cm H2O (14%, p < 0.03) and mean twitch transdiaphragmatic pressure (Tw Pdi) increased by 2.5 cm H2O at 3 months (12%, p = 0.03). There was a highly significant increase in twitch esophageal pressure (Tw Pes) (60%, p < 0.0001), which was maintained at 12 months (46% increase, p = 0.0004). No change was observed in quadriceps twitch tension in nine subjects in whom it was measured. After LVRS the ratio Tw Pes:Tw Pdi increased from 0.24 to 0.37 at 3 months (p = 0.0003) and 0.36 at 12 months (p = 008). Low values of Sn Pdi, Sn Pes, Tw Pes and a high RV/TLC ratio were the preoperative variables most predictive of improvement in shuttle walking distance. We conclude that LVRS improves diaphragm function primarily by alteration of lung volume. Patients with poor diaphragm function and high RV/TLC ratio preoperatively are most likely to benefit from the procedure.

Adult↗

Alternative EBNA1 expression in organ transplant patients.

In order to identify patients at risk for developing post-transplant lymphoproliferative disease (PTLD), a sensitive nested RT-PCR method for detection of EBNA1 gene expression in peripheral blood cells was used. EBNA1 expression in peripheral blood samples from 60 organ recipients was analyzed and compared with 24 healthy controls in a retrospective study. Overall, EBNA1-positive samples were detected at least once in 43% of the transplant patients with post-transplant lymphoproliferative disease, in 18% of the other transplant patients and in none of the healthy controls. The odds ratio for EBNA1 expression in patients with post-transplant lymphoproliferative disease was 3.42 (95% CI=1.02-11.54) compared to other transplant recipients. Together with normal EBV Q promoter initiated EBNA1 transcripts, an alternatively spliced form was expressed in peripheral blood cells in the above-mentioned transplant patients. This transcript lacks the U leader exon in the 5'-untranslated region (UTR). We have previously identified and characterized a functional internal ribosome entry site, the EBNA IRES, in the untranslated U leader exon of EBNA1. Transfection experiments with EBNA1 coding plasmids followed by Western blot showed that the EBNA IRES promotes cap-independent translation and increases the EBNA1 protein level. The alternative EBNA1 transcript lacking this function is expressed in the majority of the investigated EBNA1-positive patient samples as well as in some EBV-positive B-cell lines. Alternative splicing in this form gives EBV potential to regulate the translation of EBNA1 by modifying the 5' UTR. These findings indicate a new mechanism for EBNA1 expression in vivo.

5' Untranslated Regions↗

Tumor necrosis factor gene polymorphism and cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after cardiac transplantation. Tumor necrosis factor-alpha (TNF-alpha) may be a key factor in the development of CAV. Two bi-allelic polymorphisms associated with high TNF-alpha production have been identified in the TNF gene locus, TNFA1/2, at position -308 and TNFB1/2 at +252. We hypothesized that recipient TNFA2 and TNFB2 homozygosity is associated with the development of CAV after heart transplantation. METHODS: TNF gene polymorphisms were analyzed by multiplex fluorescent solid-phase mini-sequencing in 70 cardiac transplant recipients. Recipients homozygous for TNFA2 or TNFB2 (Group A, n = 29) were compared with recipients heterozygous or homozygous for TNFA1 and TNFB1 (Group B, n = 41). Coronary arteriography was performed annually or when indicated. Cumulative freedom from CAV and survival was calculated according to the Kaplan-Meier test. RESULTS: Mean follow-up was 3.8 +/- 0.3 years. In Group A, 11 of 29 recipients (38%) developed CAV compared with 9 of 41 (22%) in Group B (p = 0.12). Cumulative freedom from CAV at 3 years was 42% in Group A and 80% in Group B (p = 0.043). In Group A, 11 of 29 recipients (38%) died during follow-up compared with 4 of 41 (10%) in Group B (p = 0.006). Cumulative survival at 3 years was 72% in Group A and 93% in Group B (p = 0.003). CONCLUSIONS: The results suggest that TNFA2 and TNFB2 allele homozygosity is associated with cardiac allograft vasculopathy and mortality in heart transplant recipients.

Adult↗

Blunted vascular response to endothelin-a receptor blockade in cyclosporine-treated lung transplant recipients.

BACKGROUND: The majority of cyclosporine-treated transplant recipients develop hypertension. Endothelin-1 (ET-1) has been suggested to mediate cyclosporine-induced vasoconstriction when binding to ET-A receptors. We hypothesized that cyclosporine-treated lung transplant recipients have an increased basal vascular resistance and an augmented response to ET-A receptor blockade. METHODS: The selective ET-A receptor blocker BQ-123 (10 and 50 nmol/min) was infused into the brachial artery, alone or in combination with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA) (2 and 4 micromol/min) in 10 lung transplant recipients without pharmacologically treated hypertension and 8 healthy controls. Forearm blood flow (FBF) was measured by venous occlusion plethysmography and plasma levels of ET-1 were analyzed. RESULTS: Baseline forearm vascular resistance did not differ between recipients and controls (32 +/- 4 vs 42 +/- 7 mmHg/ml/min, p = 0.32). BQ-123 increased FBF in controls but not in recipients (26% +/- 9% vs 5% +/- 11% at 10 nmol/min, p = 0.043 between groups). Coinfusion of BQ-123 and L-NMMA caused a comparable decrease in FBF in recipients and controls (-26% +/- 11%, vs -34% +/- 7%). Baseline ET-1 was higher in recipients (17.2 +/- 1.1 vs 14.7 +/- 0.8 pg/ml, p = 0.038). BQ-123 infusion increased plasma ET-1 in controls but not in recipients (+24% +/- 11% vs -0.4% +/- 6.2%, p = 0.029 between groups). CONCLUSIONS: The results demonstrate that cyclosporine-treated lung transplant recipients have increased plasma levels of ET-1 and a blunted response to ET-A receptor blockade compared with healthy subjects. In contrast, we found no evidence for an increased basal vascular resistance in transplant recipients. These alterations in endothelin handling may contribute to the development of transplant-associated hypertension.

Adult↗

New-onset cardiovascular risk factors in lung transplant recipients.

BACKGROUND: Cardiovascular disease (CVD) is a common cause of morbidity and mortality after solid-organ transplantation. Both pre-existing cardiovascular risk factors in recipients and immunosuppressive drug toxicity may contribute to CVD. We sought to describe the prevalence of new-onset hypertension, hypercholesterolemia and diabetes mellitus in lung transplant recipients and to identify predisposing factors. METHODS: One hundred twenty-six patients without pre-transplant hypertension, hypercholesterolemia or diabetes were included in a retrospective descriptive study. All patients were initially on cyclosporine-based triple immunosuppression. Cumulative prevalence of new-onset hypertension, hypercholesterolemia and diabetes were calculated. A multivariate Cox regression model was used to identify independent pre-operative predictors. RESULTS: By 3 years after transplantation, 90% of patients had developed at least 1 cardiovascular risk factor and 40% developed > or = 2 risk factors. The cumulative prevalence of new-onset hypertension at 1, 3, 5 and 7 years was 45%, 65%, 67% and 72%, respectively. The corresponding prevalence for hypercholesterolemia was 16%, 33%, 48% and 58%, and for diabetes 6%, 7%, 7% and 10%, respectively. The independent pre-transplant predictors were: for hypertension, diastolic blood pressure (odds ratio: 2.1 per 10 mm Hg [95% confidence interval: 1.3 to 3.5], p = 0.005); for hypercholesterolemia, serum cholesterol level (OR: 1.8 per mmol/liter [95% CI: 1.3 to 2.5], p < 0.001); and, for diabetes, cystic fibrosis diagnosis (OR: 7.4 [95% CI: 1.6 to 35.6], p = 0.01) and blood glucose level (OR 2.2 per mmol/liter [95% CI 1.1 to 4.5], p = 0.02). CONCLUSIONS: The majority of cyclosporine-treated lung transplant recipients develop new-onset hypertension or hypercholesterolemia early after transplantation. Pre-transplant blood pressure, serum cholesterol levels and blood glucose levels are independent predictors of post-transplant hypertension, hypercholesterolemia and diabetes, respectively.

Adult↗

Comparison of lung volume reduction surgery and physical training on health status and physiologic outcomes: a randomized controlled clinical trial.

STUDY OBJECTIVES: In 1996, researchers in Sweden initiated a collaborative randomized study comparing lung volume reduction surgery (LVRS) and physical training with physical training alone. The primary end point was health status; secondary end points included survival and physiologic measurements. DESIGN: After an initial 6-week physical training program, researchers' patients were randomized to either LVRS (surgical group [SG]) with continued training for 3 months, or to continued training alone (training group [TG]) for 1 year. SETTING: All seven thoracic surgery centers in Sweden. PATIENTS: All patients in Sweden with severe emphysema fulfilling inclusion criteria for LVRS. INTERVENTIONS: Patients randomized to surgery underwent a median sternotomy, except for a few patients in whom thoracotomy or video-assisted thoracoscopy were performed. In the TG, supervised physical training continued for 1 year; in the SG, supervised physical training continued for 3 months postoperatively. MEASUREMENTS AND RESULTS: Fifty-three patients were included in each group. Six in-hospital deaths occurred after surgery (12%), and one more death occurred during follow-up. Two deaths occurred in the TG. The difference in death rates between the groups was not statistically significant. Health status, as measured by St. George Respiratory Questionnaire (SGRQ) [total scale score mean difference at 1 year, 14.7; 95% confidence interval (CI), 9.8 to 19.7] as well as by the Medical Outcomes Study Short-Form General Health Survey (physical function scale score mean difference at 1 year, 19.7; 95% CI, 12.1 to 27.3) was improved from baseline in the SG compared with the TG. FEV(1), residual volume, and shuttle walking test values also improved in the SG but not in the TG after 6 months and 12 months. CONCLUSIONS: In severe emphysema, LVRS can improve health status in survivors but is associated with mortality risk. The effects are stable for at least 1 year. Physical training alone failed to achieve a similar improvement.

Exercise Therapy↗

Off-pump CABG reduces complement activation but does not significantly affect peripheral endothelial function: a prospective randomized study.

OBJECTIVE: Cardiac surgery initiates a systemic inflammatory response, which may affect endothelial function. The aim of this study was to investigate if off-pump CABG (OPCAB) reduces the postoperative inflammatory response and affects endothelial function less than conventional on-pump CABG. DESIGN: Fifty-two patients submitted for elective CABG were included in a prospective, randomized study. Twenty-six patients were operated with, and 26 without cardiopulmonary bypass (CPB). Plasma levels of complement (C3a), cytokines (IL-8, TNF-alpha), endothelin-1 and neopterin were measured before and during surgery and 2 and 24 h after surgery. Endothelial function was assessed by forearm plethysmography and acetylcholine infusion in 30 patients 2-4 h after surgery. RESULTS: C3a and neopterin concentrations were significantly higher during and early after surgery in the CPB group while TNF-alpha and IL-8 tended to be higher in the CPB group but the difference did not reach statistical significance. Endothelial function did not differ significantly between the two groups. CONCLUSION: OPCAB reduces complement activation compared with on-pump CABG but does not significantly affect TNF-alpha and IL-8 release or endothelial function.

Acetylcholine↗

Increased arterial stiffness in cyclosporine-treated lung transplant recipients early after transplantation.

BACKGROUND: The majority of patients undergoing solid organ transplantation develop hypertension, to which cyclosporine (CsA)-induced peripheral vasoconstriction may contribute. We hypothesized that CsA-treated transplant recipients have an increased basal vascular tone and an altered response to nitric oxide. To test this hypothesis arterial resistance, non-endothelial dependent relaxation and arterial stiffness were investigated in CsA-treated lung transplant recipients within 18 months after transplantation. METHODS: In study 1, forearm blood flow (FBF) was measured by venous occlusion plethysmography at baseline and during glyceryl trinitrate (GTN) and N(G)-monomethyl-l-arginine acetate (l-NMMA) infusion in seven lung transplant recipients and nine healthy subjects. In study 2, arterial stiffness in carotid (CCA) and radial artery (RA) was measured by ultrasound (echo-tracking) in 10 lung transplant recipients, 12 healthy subjects and six patients waiting for lung transplantation. RESULTS: Basal FBF (3.1 +/- 0.2 vs. 3.0 +/- 0.3 mL/min, p = 0.79) and forearm arterial resistance (36 +/- 3 vs. 33 +/- 3 mmHg/mL/min, p = 0.60) did not differ between transplant recipients and controls. GTN infusion increased and l-NMMA decreased blood flow equally in both groups. Transplant recipients had increased arterial stiffness compared to both pre-transplant patients and healthy subjects (CCA stiffness index 11.7 +/- 1.1 vs. 8.5 +/- 0.2 and 8.6 +/- 0.6, p < 0.05 both; RA stiffness index 14.7 +/- 1.5 vs. 8.9 +/- 1.3 and 10.6 +/- 0.7, p < 0.05 both). CONCLUSIONS: Forearm blood flow and arterial resistance did not differ between healthy subjects and cyclosporine-treated lung transplant recipients early after transplantation. Increased arterial stiffness was demonstrated in transplant recipients, which may have implications for future development of transplant hypertension.

Adult↗

Mortality after mitral regurgitation surgery: importance of clinical and echocardiographic variables.

OBJECTIVES: The management of patients with mitral regurgitation (MR) constitutes a challenge due to its heterogeneity in terms of etiology and possible treatment strategies. In the present study, we sought to describe the importance of preoperative echocardiographic and clinical variables in relation to outcome 5 years after surgical treatment of MR. METHODS: The echocardiographic reports (transthoracic) from 298 patients were analyzed and the anatomic lesions were classified into one of three main groups (functional, organic degenerated with hypermobile valve or organic degenerated without hypermobility). 5-year cumulative survival was compared with the expected survival in an age- and gender-matched normal population. Risk functions were determined with a Poisson regression model. RESULTS: Operative mortality was 4.4%, with higher mortality in patients with concomitant coronary artery bypass grafting (CABG) (7.6 vs. 2.2%, P=0.03). Survival after 5 years was 65% in patients with concomitant CABG, compared with the expected 86% (P<0.001), 70 vs. 88% (P<0.001) in patients with preoperative NYHA class III/IV, while survival in patients with NYHA class I/II did not differ from the expected (90 vs. 90%, P=0.56). In patients with a hypermobile valve without CABG, postoperative survival did not differ from the expected (91 vs. 89%, P=0.92). The estimated risk ratio for death, repair versus prosthesis, was 0.57 (95% confidence interval 0.32-1.00, P=0.05). CONCLUSIONS: The present study shows that it is possible, using transthoracic echocardiography and clinical data, to identify patients with an excellent outcome. The adverse effects of severe symptomatology and replacement compared with repair are demonstrated. The findings encourage early intervention before severe symptoms occur, especially if repair is possible.

Aged↗

Effects of lung volume reduction surgery on left ventricular diastolic filling and dimensions in patients with severe emphysema.

STUDY OBJECTIVES: Data on the influence of lung volume reduction surgery (LVRS) on cardiac function and hemodynamics are scarce and controversial. Previous studies have focused mainly on right ventricular function and pulmonary hemodynamics. Here, we evaluated the effects of LVRS on left ventricular (LV) end-diastolic filling pattern, dimensions, stiffness, and performance, as well as pulmonary and systemic hemodynamics. DESIGN: A prospective, open, controlled study. PATIENTS: Patients with severe emphysema undergoing LVRS (10 patients). Patients scheduled for pulmonary lobectomy due to carcinoma (ie, the lobectomy group) served as control subjects (10 patients). MEASUREMENTS: LV dimensions and mitral flow velocities were measured by transesophageal, two-dimensional, Doppler echocardiography, and central hemodynamics were measured by a pulmonary artery thermodilution catheter. Measurements were performed during anesthesia in the supine position, before and after surgery, without and with passive leg elevation. RESULTS: Baseline cardiac index (CI) [- 21%], stroke volume index (SVI) [- 31%], stroke work index (SWI) [- 26%], and LV end-diastolic area index (EDAI) [- 15%] were significantly (p < 0.001) lower, whereas LV end-diastolic stiffness (LVEDS) did not differ in the LVRS group compared to the lobectomy group. The time from peak early diastolic filling to zero flow (E-dec time) [58%] and the deceleration slope of early diastolic filling (E-dec slope) [45%] were significantly higher (p < 0.01), whereas peak early diastolic filling velocity (E-max) [- 31%; p < 0.01] and the proportion of E-max vs peak late diastolic filling velocity (A-max) [ie, the E/A ratio] (- 27%; p < 0.001) were significantly lower compared to the lobectomy group. LVRS significantly increased CI (40%; p < 0.001), SVI (34%; p < 0.001), SWI (58%; p < 0.001), LV EDAI (18%; p < 0.001), E-max (44%; p < 0.01), A-max (15%; p < 0.05) and E/A ratio (28%; p < 0.01), decreased E-dec time (- 31%; p < 0.05) and E-dec slope (- 98%; p < 0.01), and had no effect on LVEDS. In the lobectomy group, surgery affected none of these variables. CONCLUSIONS: LV function is impaired in patients with severe emphysema due to small end-diastolic dimensions. LVRS increases LV end-diastolic dimensions and filling, and improves LV function.

Aged↗

On the allocation of cardiac allografts from blood group-O donors.

An organ allocation policy, in which hearts from blood group-O donors are used to transplant recipients with other blood groups (ABO-compatible, non-identical transplantations), may affect blood group-O patients on the waiting list. We investigated how blood group affiliation influences potential recipients on the waiting list. In the case of patients with blood group O, fewer patients were transplanted, waiting list mortality was higher and waiting time to transplantation was longer. Patients with blood group O awaiting cardiac transplantation are affected considerably by an organ allocation policy in which ABO-compatible, non-identical transplantations are performed.

ABO Blood-Group System↗