Not just any ICD device in patients with long-QT syndrome.

Patients with LQT syndrome are prone to lifethreatening arrhythmias. After surviving such an event, implantation of an ICD is indicated. There are, however, special subtle demands in the treatment of these patients. In this case report we describe our findings in a patient with LQT1 syndrome, and the pitfalls that can and must be avoided. (Neth Heart J 2007;15:418-21.).

Protein C levels in patients with Legg-Calve-Perthes disease: is it a true deficiency?

A hyper-coagulable state due to protein C deficiency has been postulated to be the cause of avascular necrosis of the capital femoral physes in Legg-Calve-Perthes disease (LCPD). In order to test this hypothesis, plasma protein C levels were analyzed from 51 unselected cases of LCPD. These were compared with a control group. Our findings showed that the levels were less than the mean for age in 38 (74.5%) of the cases, though were within the normal range. We conclude that clinical thrombosis could be triggered off in these susceptible individuals by prothrombotic insults such as passive smoking, ultimately leading to LCPD.

Unmasking accessory pathway conduction due to AV block following tricuspid valve replacement.

Atrioventricular block during radiofrequency (RF) ablation of an accessory pathway may be due to inadvertent RF damage or catheter pressure to the conduction system, or a pre-existent conduction defect. Conversely, block in the normal conduction system may unmask pre-excitation. We describe a case where total infra-Hisian block complicated tricuspid valve surgery, unmasking a hitherto undiagnosed left lateral accessory pathway.

Depression as an independent determinant of decreased heart rate variability in patients post myocardial infarction.

OBJECTIVE: Depression is associated with an increased risk of cardiac morbidity and mortality in patients following myocardial infarction (MI). Our objective was to investigate the potential role of the autonomic nervous system in mediating this detrimental effect. METHODS: The study group consisted of 95 consecutive post-MI patients without depression and 53 post-MI patients with depression. Depressive symptoms were assessed by the Beck Depression Inventory (BDI). Activity of the autonomic nervous system was assessed by analysing heart rate variability (HRV) using 24-hour ambulatory electrocardiographic recordings as obtained three months post MI. RESULTS: Higher age, female gender and left ventricular ejection fraction <0.40 were associated with lower HRV (SDANN, and very-low-frequency and low-frequency power, but not RMSSD and high-frequency power), as was depression. In the multivariate analysis, age and left ventricular ejection fraction but not gender emerged to be independently associated with HRV. After adjustment for these two covariates, depression remained significantly associated with low HRV. CONCLUSIONS: Patients with depression in the present post-MI study are characterised by decreased longer-range HRV compared with the patients without depression, independent of other clinical variables. This observation supports the concept that one of the mechanisms underlying the detrimental effect of depression on post-MI prognosis may be that depression adds to the autonomic derangement post MI.

[Cerebral infarction and myocardial infarction due to cisplatin-containing chemotherapy]. / Herseninfarct en myocardinfarct door cisplatinebevattende chemotherapie.

A 33-year-old man was treated for a testicular non-seminoma carcinoma with three different chemotherapeutic agents: bleomycin, etoposide en cisplatin (BEP). During the second course of BEP he experienced two cerebral infarctions and a myocardial infarction at almost the same time. A CT-scan of the brain revealed a subcortical infarction in the left hemisphere. Angiography of the head and neck arteries revealed an almost completely thrombotic left carotid artery. ECG recordings showed signs of transmural ischaemia of the heart and an echocardiogram demonstrated irreversible myocardial damage. The time interval between the chemotherapy and the complications suggests a cisplatin-related cause (such adverse effects are unknown with bleomycin or etoposide). Cisplatin toxicity can give rise to serious vascular complications for which several factors appear to be responsible, such as an increased thrombogenicity and vascular spasm due to hypomagnesaemia.

[Fainting caused by a neck tumor]. / Flauwvallen door een tumor in de hals.

An 86-year-old woman was admitted with progressive complaints of dizziness and the sensation of losing consciousness several times a day; this had led her to fall down on a few occasions. The patient had experienced these symptoms for a month prior to admission. Two weeks before admission her family had noticed a swelling on the left side of her neck. During admission, bradycardia and subsequently asystole occurred while she was eating or when turning her head to the left, followed by a slow junctional escape rhythm. A CT scan of the head and neck region revealed a large tumour in the left parapharyngeal space entrapping the left carotid artery. Histology disclosed a low-grade malignant non-Hodgkin lymphoma, sensitive to radiotherapy. The patient received a pacemaker and treatment of the lymphoma was uneventful. The symptomatic sinus bradycardia and asystole were caused by intermittent carotid massage by the lymphoma.

Severe haemorrhage following intrapleural streptokinase therapy for haemothorax after myocardial revascularisation with the left internal mammary artery.

Administration of intrapleural streptokinase is a well-accepted therapy for the treatment of haemothorax following myocardial revascularisation with the inner mammary artery (IMA). The present report describes a patient who developed severe hypotension with an accompanying drop in haemoglobin concentration induced by the sixth consecutive instillation of intrapleural streptokinase. This case suggests that the standard streptokinase therapy of six to eight instillations might be too much for these patients.

Defective bronchus-associated lymphoid tissue in long-term surviving rat lung allografts.

In a previous study we found that a local immune response did not develop in the bronchus-associated lymphoid tissue (BALT) of infected rat allografts. We hypothesized that the BALT in rat lung allografts was damaged after allotransplantation. Therefore, we investigated three prerequisites for a normal function of the BALT, i.e., its structure, the uptake of antigens, and the lymphocyte migration to the BALT in three groups of rats (n = 10 each): (1) Brown Norway(BN)-to-Lewis (LEW) allografts; (2) LEW-to-LEW isografts; and (3) normal LEW rats. All rats were immunosuppressed with CsA (injected on days 2 and 3). Six mo after transplantation the structure of the BALT and the uptake of intrabronchially injected carbon particles in the BALT were determined histologically; the migration of intravenously injected, fluoroscein-isothiocyanate labeled lymphocytes to the BALT was determined immunohistochemically. In the allografts the BALT was defective in all three investigated aspects. It was reduced in size and lymphocyte density and was largely replaced by fibrous tissue. Twenty-four h after administration no carbon particles and only a few labeled lymphocytes were found in the BALT. In contrast, in the syngeneically transplanted and nontransplanted lungs the BALT consisted of a large and dense collection of lymphocytes. In these BALTs large numbers of carbon particles and labeled lymphocytes were found. In conclusion, after allogeneic transplantation the BALT in the lung becomes defective in structure and function. The BALT is most likely damaged by rejection, since the BALT is syngeneic lung transplants was perfectly normal.

Inadequate antibody response against respiratory viral infection in long-surviving rat lung allografts.

Lung transplant recipients suffer from a high number of viral infections. It has been suggested that the defense against viral infections is impaired in lung transplants. Therefore, we investigated in rat lung transplants whether antibody responses against an intrapulmonary viral infection were impaired in 3 groups of rats with: (1) BN-to-LEW allogeneic lung transplants, (2) LEW-to-LEW syngeneic lung transplants, and (3) nontransplanted LEW lungs. All rats (including those with nontransplanted, normal lungs) were treated with cyclosporine on days 2 and 3 after operation; this treatment is adequate to induce permanent graft acceptance of the allografts. Six months after transplantation, viral infections with Sendai virus (parainfluenza type I) were induced intratracheally. At day 0, immediately before infection, and at days 4, 7, 21, and 56 after infection, 4 rats in each group were killed for histological evaluation of the lungs. The number of antibody-positive cells in the bronchus-associated lymphoid tissue (BALT) in the lungs and in the spleen, and presence of the virus in the lungs were determined by immunohistology. Serum antibody titers were followed for 56 days after infection. The allogeneically transplanted lungs failed to respond adequately against the virus: the number of antibody-positive cells in the BALT did not increase after infection, serum antibody titers were hardly detectable, and virus was present in the airways of the lungs up to day 21 after infection. In contrast, in the syngeneically and nontransplanted lungs, the number of antibody-forming cells in the BALT increased steeply until day 7, serum antibody titers rose until day 14, and virus could be detected only on day 4 after infection. This study shows that in rat lung allografts, both the local antibody production in the BALT and the systemic antibody response against a respiratory viral infection are inadequate. As a consequence, the virus is present longer in these allografted lungs and can exert its damaging effect over a longer period of time. These results may explain why lung transplants are so susceptible to viral infections.

Distinct phenotypes of infiltrating cells during acute and chronic lung rejection in human heart-lung transplants.

To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung rejection, as diagnosed by clinical data and histopathological investigation. TBBs without rejection and normal lung tissue specimens served as controls. Distinct phenotypes of inflammatory cells were found in acute and chronic lung rejection. T cells were present both in acute and in chronic rejection, but did not differentiate between them. In contrast, B cells with antibody deposition were mainly present in chronic rejection and not in acute rejection. Activated macrophages were present only in acute rejection and not in chronic rejection. In nonrejecting lung transplants, perivascular infiltrating cells were virtually absent. In the biopsy specimen, vessels had to be available for analysis, because the cell phenotypes were best recognized in perivascular infiltrates. The analysis of specific phenotypes of inflammatory cells by immunohistochemistry supports the diagnosis of acute and chronic lung rejection, in particular in those cases in which TBB provides limited tissue without airways.

Respiratory viral infections aggravate airway damage caused by chronic rejection in rat lung allografts.

Airway damage resulting in bronchiolitis obliterans occurs frequently in patients after heart-lung and lung transplantation. Generally, chronic rejection is assumed to be the most important cause of bronchiolitis obliterans. However, viral infections might also be potential causes of airway damage after lung transplantation. In the present study, we investigated whether viral infections could induce airway damage in rat lung transplants in the absence or presence of chronic rejection. We compared the histopathology of the airways in 3 groups of rats: (1) nontransplanted LEW lungs, (2) LEW-to-LEW syngeneic lung transplants, and (3) BN-to-LEW allogeneic lung transplants. Nontransplanted and transplanted rats were treated with CsA to induce permanent graft acceptance of the allografts. Six months after transplantation, 4 noninfected rats of each group were killed for histological investigation (another 4 noninfected allografted rats were killed 56 days later). The remaining 16 rats in each group were infected with Sendai virus (parainfluenza type 1) intratracheally. These rats were killed for histological investigation 4, 7, 21, and 56 days after infection. In the lungs of the noninfected rats of the nontransplanted and syngeneically transplanted groups, airway changes were absent. After viral infection in these lungs, mild inflammation developed in the airways that was transient and completely resolved by day 56 after infection. In contrast, in the allogeneically transplanted lungs the viral infection caused severe and permanent damage of the airways. In the bronchioles and the large airways throughout the allogeneic lung transplants, inflammation with epithelial necrosis and formation of granulation tissue was present. On day 56 after infection, the bronchioles showed scarring in the submucosa and obliteration of the lumen, typical features of bronchiolitis obliterans. This study shows that a respiratory viral infection aggravates the airway damage in rat lung allografts with chronic rejection. The findings suggest that viral infections and chronic rejection play a synergistic role in the development of bronchiolitis obliterans after human heart-lung and lung transplantation: the virus infection may stimulate chronic rejection and rejection may hamper the local defense against the virus.

Replacement of dendritic cells in the airways of rat lung allografts.

It is unknown whether dendritic cells are able to migrate normally from the recipient into the allogeneic lung graft. Using monoclonal antibodies to major histocompatibility complex class II antigens (OX6 for both donor and recipient types; HIS19 for recipient type), we studied the replacement of donor dendritic cells by recipient type cells in rat lung allografts that are indefinitely accepted with a short course of cyclosporine early after transplantation. The recipient dendritic cells started to migrate into lung allografts early (by 1 wk) after transplantation. Donor dendritic cells in the grafts were replaced by recipient cells during the first 2 months after transplantation. Dendritic cells in the perivascular tissue were replaced quickly, most of them within 1 wk, whereas those in the alveolar septa were replaced slowly. In the lung allograft surviving 2 or more months, the normal phenotypic heterogeneity of dendritic cells was preserved. Recipient dendritic cells accumulated in dense peribronchial aggregates that remained 6 months. The dendritic aggregates were associated with late airway changes in allografted lungs. The abnormal accumulation of dendritic cells peribronchially might be related to an abnormal mucosal immune response or a chronic rejection process.

Reduced antibody responses after immunization in rat lung transplants.

Pulmonary infections occur so frequently in recipients of lung transplants as well as of combined heart and lung transplants that it has been suggested that the function of the defense system in lung transplants is impaired. Therefore, we investigated in rats whether antibody responses against intrapulmonary antigens were impaired at various time points after transplantation. Antibody responses were induced in lungs of four experimental groups. Group 1: normal lungs (LEW); Group 2: hilar-stripped (sham-operated) lungs (LEW); Group 3: syngeneic lung transplants (LEW-to-LEW); Group 4: allogeneic lung transplants (BN-to-LEW). The operations were performed on the left lungs. All rats (including those with normal lungs) were treated with cyclosporine on Days 2 and 3 after operation, which treatment is adequate to induce permanent graft acceptance of the allografts. Rats were immunized 7, 10, 14, 21, and 28 days and at 6 months after operation with sheep red blood cells, injected selectively into the bronchus of the left lung. The resulting serum antibody titers were detected with a hemolysis assay. After immunization on Day 7, no antibody responses could be detected in all hilar-stripped and transplanted rats, whereas responses were normal in two allografted rats immunized in the nontransplanted right lung. After immunization on Day 14, responses had returned to normal in hilar-stripped rats, whereas they were still impaired in the transplanted rats. After immunization on Day 28, responses were almost normal in all rats and remained so until 6 months after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Late airway changes caused by chronic rejection in rat lung allografts.

Airway disease after lung or heart-lung transplantation is one of late major complications, affecting the prognosis of the transplants. Little is known about the causes of airway changes. We performed rat lung transplantation and investigated the late airway changes of the long-term surviving lung grafts: allografts, BN to Lewis; isografts, BN to BN rat. All recipients were treated with CsA. We found airway changes, i.e., mucosal ulceration, granulation, submucosal fibrosis, which was located in the large airways, in four of five allografted lungs. The lung isografts showed no pathological abnormalities. Immunopathological studies disclosed the localized expression of MHC class II antigens on the bronchial epithelium of the large airways where recipient type dendritic cells accumulated in the submucosa and CD4 positive predominant lymphocytes infiltrated. These findings support the idea that the late airway changes in lung transplants are caused by immunologically mediated chronic rejection.

Influence of interrupted pulmonary lymph drainage on antibody responses in hilar-stripped lungs.

Lung transplantation interrupts hilar lymphatics. This may have an impact on immune responses to antigens entering the lung because the antigens cannot reach the lung-associated lymph nodes where the immune response is generated. We investigated the interruption and regeneration of lymphatics and the influence of this on antibody responses after hilar stripping in rats in three experiments: (1) visual detection of regenerated hilar lymphatics by chromolymphography, (2) observation of transport of carbon particles from the lung to the lung-associated lymph nodes, and (3) assessment of antibody responses after lung immunization with sheep red blood cells. The findings showed that hilar lymphatics were interrupted by hilar stripping and regenerated from day 7 after operation. Transport of particles to the lung-associated lymph nodes was blocked during the first week after operation but returned to normal values thereafter. Serum antibody titers were absent or low in the rats immunized on days 7 and 10 after hilar stripping; subsequently antibody responses gradually recovered in 1 month. We conclude that antibody responses to antigens in hilar-stripped lungs are impaired as long as the antigens cannot be transported through lymphatics from the lung to the lung-associated lymph nodes. These findings can explain in part why pulmonary infections occur so frequently in the initial weeks after lung transplantation.