Indocyanine green plasma disappearance rate during the anhepatic phase of orthotopic liver transplantation

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI]=0.8-2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account.

Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation

Oxygen-sensitive 3He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO2) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acqiured on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n = 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (-1.75 mbar/s versus -0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients.

Percutaneous autologous venous valve transplantation: short-term feasibility study in an ovine model

BACKGROUND: Limited experience with bioprosthetic venous valve percutaneously inserted into femoral veins in 15 patients has been promising in short-term results only to show disappointing long-term results. Percutaneous autogenous venous valve (PAVV) transplantation was explored in an ovine model as a possible alternative treatment. METHODS: PAVV consisted of a vein segment containing a valve that was attached to a stent template. The stent templates (n = 9) were designed and hand made in our research laboratory. They consist of two stainless steel square stents 13 or 15 mm in diameter to fit the ovine jugular veins (JV), which ranges from 10 to 15 mm in diameter. A valve-containing segment of JV was harvested and attached with sutures and barbs inside the stent template (n = 9). The valve devices were then manually folded and front loaded inside the 4 cm chamber of the 13F delivery sheath and delivered into the contralateral JV by femoral vein approach. Transplanted PAVVs were studied by immediate and 3 months venograms. Animals were euthanized at 3 months, and jugular veins harvested to perform angioscopic evaluations in vitro. RESULTS: PAVV transplantation was successful in all nine animals. Good valve function with no reflux was observed on immediate and 3 months venograms in eight valves. The transplanted maximal JV diameter ranged from 10.2 mm to 15.4 mm (mean 13.1 +/- 1.5 mm). Venoscopic examination revealed intact, flexible, nonthickened valve leaflets in eight specimens. One PAVV exhibited normal function of one leaflet only; the other cusp was accidentally cut during the transplantation procedure. All transplanted autologous valves were free of thrombus and incorporated into the vein wall of the host vessel. CONCLUSION: This study demonstrated that autogenous valve transplants remained patent and competent without long-term anticoagulation for up to 3 months. The percutaneous autogenous venous valve may provide in future minimally invasive treatment for patients with chronic deep venous insufficiency, but long-term studies need to be done to document its continued patency and function.

Role of beta1-, beta2-, and beta3-adrenoceptors in contractile hypersensitivity in a model of small bowel transplantation

BACKGROUND: Chronic extrinsic denervation induced by small bowel transplantation (SBT) results in adrenergic hypersensitivity in rat ileum. This study evaluated the role of neuronal and/or muscular beta1-, beta2-, and beta3-adrenoceptor (AR) mechanisms on contractility. METHODS: Ileal longitudinal muscle strips from Lewis rats (n = 6 rats per group, 8 strips per rat): naive controls (NC), 4 months after sham operation (SC) or after syngeneic orthotopic SBT were studied in vitro. Spontaneous contractile activity and dose responses (10(-8)-10(-4) mol) to isoprenaline (IP), a nonspecific beta-AR agonist were studied with or without selective antagonists (10(-5) mol), for beta1- (atenolol), beta2- (ICI 118551), or beta3- (SR 59230A) AR subtypes in the presence or absence of tetrodotoxin (TTX; 10(-6) mol; nerve blocker). RESULTS: pEC50 (neg log of EC50, which is the concentration where 50% of inhibition was observed) of IP was 7.2 +/- 0.2 (mean value +/- SEM) in SBT vs 6.3 +/- 0.1 in SC and 6.3 +/- 0.2 in NC (both P < .05 vs SBT), reflecting adrenergic hypersensitivity. Beta1- and beta2-AR blockade induced a TTX-sensitive right shift of the curve only in SBT and normalized pEC50 values from 7.2 +/- 0.2 to 6.4 +/- 0.1 and 7.2 +/- 0.2 to 6.6 +/- 0.1, respectively (P < .05). Beta3-AR blockade shifted the curve independent of the presence of TTX to the right in all groups (all P < .05). CONCLUSIONS: In rat ileum, adrenergic inhibition of contractility was dependent on muscular beta3-AR pathways, whereas posttransplant hypersensitivity was due to upregulated neuronal beta1- and beta2-AR mechanisms that were inactive before SBT.

Upregulation of endothelin converting enzyme-1 in host liver during chronic cardiac allograft rejection

Endothelin regulates cytokine expression in vitro and in vivo. This study investigated the effects of chronic allograft rejection on hepatic endothelin-converting enzyme-1 (ECE-1) gene expression and endothelin-1 (ET-1) plasma clearance. Using the Lewis-F344 minor histocompatibility mismatch model of heterotopic cardiac transplantation, hepatic ECE-1 gene expression was measured by real-time polymerase chain reaction and host plasma clearance of ET-1 was measured 8 weeks after transplantation in the absence of immunosuppression. In animals undergoing allograft rejection, hepatic ECE-1 gene expression increased 2-fold (P < 0.05), whereas no effect of rejection on ET-1 clearance from plasma was observed. In summary, upregulation of ECE-1 gene expression occurs in the liver of the host during chronic allograft rejection. Because the liver represents both a key organ for cytokine production and for endothelin metabolism, increased hepatic ECE-1-mediated ET-1 synthesis may contribute to host responses and cytokine production during allograft rejection.

Posttraumatic stress disorder after implantation of a mechanical assist device followed by heart transplantation: evaluation of patients and partners

AIM: We sought to investigate the prevalence of posttraumatic stress disorder, anxiety, and depression in patients and their partners after implantation of a mechanical assist device as a bridge to heart transplantation. METHODS: This was a retrospective assessment of 41 patients (age 46.3 +/- 12.0 years; male-female ratio, 38:3; time since transplantation, 55.3 +/- 34.2 months [range, 7-122 months) and 27 partners (male-female ratio 2:25) by standardized instruments (Impact of Event Scale, Hospital Anxiety and Depression Scale), in 2 University Heart Transplant Centers (Vienna, Austria, Munster, Germany). The duration of the support systems (MicroMed DeBakey-VAD in 17 patients, Novacor in 10, Thoratec in 8, TCI HeartMate in 5, and Berlin Heart Incor in 1 patient) ranged from 28 to 711 (176 +/- 146) days. RESULTS: None of the patients, but 23% of the partners (n = 6), met the criteria for posttraumatic stress disorder (Maercker cutoff >0). The Impact of Event Scale (IES) sum scales differed significantly between the 2 groups (21.2 +/- 15.1, mean +/- SD) for the patients versus 38.1 +/- 27.8 for the partners, respectively; P = .001). Two percent of the patients, but 19% of the partners, showed mild to moderate depression; 4% of patients, but 23% of their partners, reported mild to moderate anxiety. None of the results were significantly influenced by the time since transplantation, patient age, diagnoses, type of assist device, or indication for heart transplantation. CONCLUSIONS: Despite patients being much closer to a life threat, their partners experience significantly more psychologic distress even in the long run. Our findings highlight the need for attention to the supporting persons.

[Survival, clinical data and quality of life 10 years after heart transplantation: a prospective study]

AIM: To study prospectively patients after heart transplantation with respect to quality of life, mortality, morbidity, and clinical parameters before and up to 10 years after the operation. METHODS: Sixty patients (47.9 +/- 10.9 years, 57 men, 3 women) were transplanted at the University of Vienna Hospital, Department for Heart and Thorax Surgery and were included in this study. They were assessed when set on the waiting list, then exactly one, 5 and 10 years after the transplantation. The variables evaluated included physical and emotional complaints, well-being, mortality and morbidity. In the sample of patients who survived 10 years (n = 23), morbidity (infections, malignancies, graft arteriosclerosis, and rejection episodes) as well as quality of life were evaluated. RESULTS: Actuarial survival rates were 83.3, 66.7, 48.3% at 1, 5, and 10 years after transplantation, respectively. During the first year, infections were the most important reasons for premature death. As a cause of mortality, malignancies were found between years 1 and 5, and graft arteriosclerosis between years 5 and 10. Physical complaints diminished significantly after the operation, but grew significantly during the period from 5 to 10 years (p < 0.001). However, trembling (p < 0.05) and paraesthesies (p < 0.01) diminished continuously. Emotional complaints such as depression and dysphoria (both p < 0.05) increased until the tenth year after their nadir at year 1. In long-time survivors, 3 malignancies (lung, skin, thyroidea) were diagnosed 6 to 9 years postoperatively. Three patients (13%) had signs of graft arteriosclerosis at year 10; 9 (40%) patients suffered from rejection episodes during the course of 10 years. There were no serious rejection episodes deserving immediate therapy. Quality of life at 10 years is good in these patients. CONCLUSIONS: Heart transplantation is a successful therapy for patients with terminal heart disease. Long-term survivors feel well after 10 years and report a good quality of life.

Long-term effects of heart transplantation: the gap between physical performance and emotional well-being

The purpose of our study was to assess physical and emotional factors in heart transplant patients. A prospective design was used to compare patients' physical symptoms, emotional complaints, and restrictions at admission to the waiting list, immediately after, and 1 and 5 years after heart transplantation. Thirty-three patients were included (30 male, 3 female) in the study. Their mean age at admission was 48 +/- 10.2 years. Of these, 23 suffered from cardiomyopathy, 8 from coronary heart disease, and 2 from valvular insufficiency. At admission, the patients suffered from symptoms of cardiac insufficiency, and were restricted in sports, gardening, hobbies, sexual life, job, food-intake, and mobility. More than three-fourths rated their physical and emotional status as moderate to poor. Emotionally, they suffered from irritability, restlessness, depression, psychic lability, lowered drive, lack of social contact, low self-esteem, and anxiety. At the end of rehabilitation (4-8 weeks after the operation), all physical and emotional complaints, as well as restrictions had significantly decreased (p < 0.0001 to p < 0.001), except for trembling, numbness of hands/feet, and food-intake. One year postoperatively, patients reported even fewer physical complaints (p < 0.01). Three-fourths rated their physical and emotional status good or excellent. Five years postoperatively--in contrast to physical status, restrictions, and physical complaints--the emotional complaints had increased significantly (p < 0.0001). Patients reported excellent physical performance up to 5 years postoperatively. On the other hand, the study revealed that their emotional well-being had significantly deteriorated from 1 to 5 years postoperatively. Attention should, therefore, not only be paid to the good physical health of the survivors, but also to the worsening of their emotional status.

Patients benefit--partners suffer? The impact of heart transplantation on the partner relationship

Terminal heart disease affects not only the patient, but also members of the patient's family, and especially the spouse. The aim of this prospective study of 26 couples was to collect information about the impact of heart transplantation on the partner relationship. Data were collected from patients and spouses when the patients were placed on the waiting list for transplantation, 1 year postoperatively, and 5 years postoperatively. The Family Assessment Measure (FAM III), a self-report instrument that provides quantitative indices of family functioning on seven interacting dimensions, was used. In the course of the transplant process, both patients and spouses reported a significant deterioration in the partner relationship in general. While patients perceived only one clear-cut point of conflict communication about emotions - as crucial, the spouses reported a significant worsening in role performance, communication, emotional involvement, and values and norms. These changes were discernible 1 year after transplantation and persisted for at least 5 years. We conclude that heart transplantation has a significant negative impact on the partner relationship 1-5 years after transplantation. Consequently, more attention should be paid to all aspects of the partner relationship in a holistic approach to the treatment of heart transplant recipients and their partners.

Expression of CD95 on mature leukocytes of MRL/lpr mice after transplantation of genetically modified bone marrow stem cells

Bone marrow transplantation (BMT) is commonly used for the treatment of severe haematological and immunological diseases. For instance, the autoimmune lymphoproliferative syndrome (ALPS) caused by a complete expression defect of CD95 (Fas, APO-1) can be cured by allogeneic BMT. However, since this therapy may not generate satisfactory results when only partially compatible donors are available, we were interested in the development of a potential alternative treatment by using lentiviral gene transfer of a normal copy of CD95 cDNA in hematopoietic stem cells. Here, we show that this approach applied to MRL/lpr mice results in the expression of functional CD95 receptors on the surface of lymphocytes, monocytes, and granulocytes. This suggests that correction of CD95 deficiency can be achieved by gene therapy.

The accuracy of FAST in relation to grade of solid organ injuries: a retrospective analysis of 226 trauma patients with liver or splenic lesion

BACKGROUND: This study investigated the role of a negative FAST in the diagnostic and therapeutic algorithm of multiply injured patients with liver or splenic lesions. METHODS: A retrospective analysis of 226 multiply injured patients with liver or splenic lesions treated at Bern University Hospital, Switzerland. RESULTS: FAST failed to detect free fluid or organ lesions in 45 of 226 patients with spleen or liver injuries (sensitivity 80.1%). Overall specificity was 99.5%. The positive and negative predictive values were 99.4% and 83.3%. The overall likelihood ratios for a positive and negative FAST were 160.2 and 0.2. Grade III-V organ lesions were detected more frequently than grade I and II lesions. Without the additional diagnostic accuracy of a CT scan, the mean ISS of the FAST-false-negative patients would be significantly underestimated and 7 previously unsuspected intra-abdominal injuries would have been missed. CONCLUSION: FAST is an expedient tool for the primary assessment of polytraumatized patients to rule out high grade intra-abdominal injuries. However, the low overall diagnostic sensitivity of FAST may lead to underestimated injury patterns and delayed complications may occur. Hence, in hemodynamically stable patients with abdominal trauma, an early CT scan should be considered and one must be aware of the potential shortcomings of a "negative FAST".