[Acute coronary syndrome after diclofenac induced coronary spasm]. / Akutes Koronarsyndrom durch Diclofenac induzierte Koronarspasmen.

We report about a 67-year old man, who was submitted to our clinic with acute coronary syndrome. The cardiac catheterization showed a proximal thrombus in the left anterior descending (LAD). The other coronary arteries did not have significant lesions. After percutaneous transluminal coronary angioplasty with stent-implantation into the proximal LAD the patient remained clinically stable. Cardiac enzymes confirmed no myocardial necrosis. Three days after the acute coronary syndrome the patient developed a podagra, which was treated with colchicinum, diclofenac and local cooling. Five hours after initial therapy the patient developed severe symptoms of angina pectoris and electrocardiographical signs of an acute posterior and anterior myocardial infarction. Immediate coronary angiography demonstrated extended vasospasm of the right coronary artery. Intracoronary application of verapamil and nitroglycerin resolved the coronary spasm. The patient reported about a self-indicated application of diclofenac six hours before hospital admission. This case demonstrates that oral application of diclofenac can provoke coronary vasospasm.

[Bland-White-Garland syndrome in an adult]. / Das Bland-White-Garland-Syndrom im Erwachsenenalter.

We report about a 47-year-old woman, who presented with a history of cardiac failure. Echocardiography showed an impaired left ventricular function, clinically significant mitral regurgitation and pulmonary hypertension. Diagnosis of a Bland- White-Garland syndrome was made by coronary angiography. Subsequent therapy consisted of ligation of the anomalus origin of the left coronary artery, implantation of a Mammaria interna graft to the left coronary artery and replacement of the mitral valve by a mechanical prosthesis. One year after operation, left ventricular function was still impaired. At a 3-year follow-up, left ventricular function improved continuously.

[Effect of drug therapy on frequency of adequate discharges of implanted cardioverter defibrillator]. / Vliianie medikamentoznoi terapii na chastotu motivirovannogo srabatyvaniia implantiruemogo kardiovertera-defibrilliatora.

Effect of concomitant antiarrhythmic therapy (amiodarone, sotalol, beta-adrenoblockers, calcium antagonists) on frequency of adequate discharges of implantable cardioverter defibrillators was studied in 149 patients. Amiodarone and sotalol significantly decreased frequency of life threatening arrhythmias (p=0.018) and defibrillator discharges(p=0.028). Beta-blockers and calcium antagonists did not affect significantly frequency of discharges. None of the antiarrhythmic drugs caused modification of ventricular tachycardia sufficient to prevent its recognition. These results can be utilized in recommendations of antiarrhythmic drug therapy in patients with implanted cardioverter defibrillators.

[Unmotivated malfunction of implanted cardioverter-defibrillator and ways of its correction]. / Nemotivirovannoe srabatyvanie implantiruemogo kardiovertera-defibrilliatora i vozmozhnye puti ego ustraneniia.

The study included 149 patients with implanted cardioverters-defibrillators (CD) at high risk of development of ventricular tachyarrhythmia. It was found that unmotivated malfunction of CD occurs in supraventricular tachycardia, when a short episode of ventricular tachycardia spontaneously ends before CD starts to work, when T-wave is mistaken for ventricular contraction, in defective isolation, electrode dislocation. A method to reduce frequency of CD malfunction is proposed. To prevent unmotivated discharges it is recommended to use attendant drug therapy, upgrading equipment and algorithms of tachyarrhythmia detection, early correction of myocardial ischemia and electrolyte disorders.

[Predictors of life-threatening arrhythmias in patients with implanted cardioverters-defibrillators]. / Prediktory vozniknoveniia zhizneugrozhaiushchikh narushenii ritma kardioverterami-defibrilliatorami.

To determine and analyze factors influencing onset of life-threatening cardiac arrhythmia in patients with implanted cardioverters-defibrillators (CD), 149 patients were examined by 70 characteristics including results of medical examination prior to implantation of CD, data of regular postoperative outpatient control. It was found that onset and discharge frequency of CD depended much on cardiac failure of NYHA functional class III-IV (p = 0.0423), induced ventricular tachycardia in electrophysiological test (p = 0.029), myocardial infarction (MI) without operative revascularization (p = 0.042) or 2 and more MIs irrespective of revascularization (p = 0.002), supraventricular tachycardia (p = 0.041). Groups of high risk to develop life-threatening arrhythmia among patients with implanted CD were selected. The results of the investigation can be used for the design of recommendations how to reduce the probability of ventricular tachyarrhythmia and how to lessen the frequency of CD operation and raise quality of life for patients with implanted CD. Moreover, the findings can be used for specifying indications for CD implantation.

[Pullback atherectomy. An alternative procedure in the treatment of coronary stenosis and in-stent restenosis]. / Pullback-Atherektomie: Ein alternatives Verfahren zur Behandlung von Koronarstenosen und in-Stent-Restenosen.

Optimized directional coronary atherectomy (DCA) has shown significantly superior acute and long-term results compared to conventional balloon angioplasty (BA). Nevertheless DCA has remained a niche application due to specific procedural aspects. The pullback atherectomy catheter (PAC), developed to retrieve atheromatous plaque material, is an alternative debulking device. We report on clinical and angiographic experience in 55 consecutive patients, in whom de novo lesions (35 pts) as well as instent restenoses (17 pts) were treated. The minimal luminal diameter (MLD, mm) rose after PAC and additional BA from 1.06 +/- 0.53 to 2.68 +/- 0.48 and from 1.10 +/- 0.48 to 2.55 +/- 0.49 mm, respectively. A stenosis reduction from 69 +/- 13 to 19 +/- 16 and from 64 +/- 15 to 16 +/- 10%, resp., could be documented. After 3-6 months a complete angiographic follow-up showed MLD values of 2.01 +/- 0.69 and 1.88 +/- 0.61 mm. Nine of 35 (26%) vs. 5 of 17 (29%) pts developed significant restenosis at the treated site (diameter stenoses > 50%). Stent implantation was necessary to achieve an optimal acute angiographic result or due to dissection in 17 vs. 5 pts. Major cardiac events did not occur; however, two restenosed coilstents were removed by PAC. With the pullback atherectomy catheter, a safe and effective alternative device is available for the treatment of coronary lesions and also of in-stent restenosis. Promising short and acceptable long-term results are comparable to those of other debulking procedures.

Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells.

BACKGROUND: Cytomegalovirus (CMV) is known as a common pathogen causing infections after lung transplantation. Rapid diagnosis of CMV infection is important for the initiation of a specific treatment. OBJECTIVE: Evaluation of methods for the rapid diagnosis of CMV pneumonitis. METHODS: The detection rates of CMV DNA in bronchoalveolar lavage (BAL) and bronchial brushes by polymerase chain reaction (PCR), of viral antigens (p52 and IE1) in BAL and of pp65 antigen in peripheral blood leukocytes were compared to the clinical status after lung transplantation. In 28 patients, 105 BAL, 96 blood samples and 14 brushes were analyzed. RESULTS: In 6 patients, a total of eight episodes of CMV pneumonitis occurred. Five of the 6 with positive CMV antigens in BAL (p52 or IE1) showed signs of CMV pneumonitis. All episodes of CMV pneumonitis were detected by the PCR of BAL cells. Fourteen samples positive for CMV pp65 antigen in blood were negative in BAL PCR. In these cases, no clinical signs of pulmonary CMV infection occurred. Overall sensitivity, specificity, and positive and negative predictive values for the detection of CMV pneumonitis by PCR of BAL cells were 100, 98.9, 88.9 and 100%, respectively. In brush samples, PCR did not provide additional information to the results of the PCR of BAL cells. CONCLUSIONS: PCR of DNA from BAL cells is suitable for reliable and rapid detection of CMV pneumonitis.

Adhesion molecules in patients after lung transplantation.

Leukocyte adhesion molecules, such as intercellular adhesion molecule (ICAM)-1 and its ligands, are involved in inflammatory processes of the lung. For ICAM-1, differential expression during different kinds of complications after transplantation has been proposed. We analyzed the role of ICAM-1, CD18, CD11a, CD11b, and CD11c during episodes of rejection or infection in patients after lung transplantation and compared the results to episodes without apparent complication. A total of 98 bronchoalveolar lavage (BAL) samples and 90 serum samples were analyzed. ICAM-1, CD18, CD11a, CD11b, and CD11c expressions were detected immunocytochemically on alveolar macrophages. Soluble ICAM-1 was quantified in serum and BAL. In the control group, 49.8 +/- 18% of macrophages stained positive for CD11b. During rejection, the mean of cells showing CD11b on the surface was significantly higher (64.6 +/-11.4%) with no difference compared to episodes of infection (59.7 +/-22.7). All other epitopes were not expressed differently with regard to a normal clinical course or episodes of infection and rejections. In summary, assessment of ICAM-1 and corresponding ligands did not allow for a reliable discrimination between episodes of rejection or infection in lung transplantation.

Eosinophilic alveolitis in BAL after lung transplantation.

Lung transplantation has become a therapeutic option for patients with end stage lung disease. However, outcome after transplantation is complicated by episodes of rejection and infections. Bronchoalveolar lavage is a valuable tool in monitoring patients after transplantation, since it allows the detection of pathogens. A marker specifically indicating rejection from changes in BAL fluid has not been found yet. Especially changes in differential cell count, like lymphocytosis or an increase in polymorphnuclear granulocytes, are unspecific. The role of high eosinophil levels in BAL has not been elucidated yet. We analyzed 25 BAL samples and clinical data of 4 patients who underwent lung transplantation and presented with recurrent episodes of eosinophilic alveolitis in BAL. All patients demonstrated a deterioration of clinical condition, lung function, and blood gas analysis during times of eosinophilia in BAL, compared to previous examinations. In all cases, eosinophilia in BAL was accompanied by rejection. All patients were finally treated with high doses of steroids, resulting in improvement of all parameters. Eosinophilia was not associated with significant changes in the IL-5 concentration in BAL or the pattern of IL-5 expression in BAL cells. In conclusion, eosinophilic alveolitis may indicate acute rejection in patients after lung transplantation, if other causes of eosinophilia are excluded.

Bronchoalveolar lavage in lung transplantation. State of the art.

Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) has become a crucial tool in the management of lung transplant recipients. Detection of pulmonary infectious pathogens by culture, cytology, and histology of BAL, protected brush specimens, and transbronchial biopsies (TBB) is highly effective. Morphologic and phenotypological analyses of BAL cells may be suggestive for certain complications after lung transplantation. For interpretation of BAL findings, the natural course of BAL cell morphology and phenotypology after lung transplantation must be considered. During the first 3 months after pulmonary transplantation, elevated total cell count in BAL and neutrophilic alveolitis are common, representing the cellular response to graft injury and interaction of immunocompetent cells of donor and recipient origin. With increasing time after transplantation the CD4/CD8 ratio decreases due to lowered percentages of CD4 cells in BAL. During bacterial pneumonias, the cellular profile of BAL is characterized by a marked granulocytic alveolitis. Lymphocytic alveolitis with a decreased CD4/CD8 ratio is suggestive of acute rejection, but is also found in viral pneumonias and obliterative bronchiolitis. In the case of a combined lymphocytosis and neutrophilia without any evidence of infection, obliterative bronchiolitis should be considered. Functional analyses of BAL cells can give additional information about the immunologic status of the graft, even before histologic changes become evident but have not been established in routine transplant monitoring. However, functional studies suggest an important role of activated, alloreactive and donor-specific T lymphocytes in the pathogenesis of acute and chronic lung rejection. Investigations of soluble components in BAL have given further insight into the immunologic processes after lung transplantation. In this overview, the characteristics of BAL after lung transplantation will be summarized, and its relevance for the detection of pulmonary complications will be discussed.

Gene expression of profibrotic mediators in bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome (BOS) develops in one-third of lung transplant recipients. A fibroproliferative process involving mesenchymal cells is observed histopathologically. In order further to evaluate the pathomechanisms of BOS, the gene expression of platelet-derived growth factor (PDGF)-B and transforming growth factor (TGF)-beta 1 in bronchoalveolar lavage (BAL) cells of six lung transplant recipients and appropriate controls was studied. Equal amounts of total RNA were submitted to semiquantitative reverse transcription/polymerase chain reaction (RT-PCR), amplifying actin, PDGF-B and TGF-beta 1 using established protocols and primer sets. The signal/actin ratio was calculated based on laser densitometry measurements. TGF-beta 1 transcripts were detected in all samples, and a slight increase in BOS patients was observed. PDGF-B mRNA was increased in BAL samples from BOS patients compared to unaffected recipients and controls. Plotting the FEV1 in percent of vital capacity and the PDGF expression in BOS patients revealed an increased PDGF signal preceding lung function deterioration. The data were consistent with the hypothesis based mainly on in vitro findings that PDGF and TGF-beta contribute to the development of BOS.

[Analysis of lymphocyte populations with flow cytometry in routine bronchoalveolar lavage diagnosis: comparison of a 3-color method with the alkaline phosphatase anti-alkaline phosphatase immunohistochemistry]. / Durchflusszytometrische Analyse der Lymphozytenpopulationen in der BAL-Routine-Diagnostik: Vergleich einer 3-Farben-Methode mit der APAAP-Immunfärbetechnik.

BACKGROUND: Identification of lymphocyte phenotypes in bronchoalveolar lavage (BAL) plays a crucial role in the diagnosis of interstitial lung disease. Cells staining positive for specific monoclonal antibodies may be detected by immunocytochemistry or flow cytometry (FCM). The present study compares a three-colour FCM-approach to a standard APAAP protocol for immunocytochemistry. METHODS: BAL-specimens of 22 patients with various lung diseases were investigated. Inclusion criteria was a lymphocytosis of > 10% of all BAL-cells. After the preparation of cytocentrifuge slides, staining was performed with monoclonal antibodies to CD3, CD4 and CD8 following the APAAP-protocol. FCM-analysis was performed with the following panel of conjugates: CD3-FITC, CD4- or CD8-PE, CD45-perCP. Lymphocytes were gated by their SSC/CD45 characteristics. T-helper and T-suppressor percentages were evaluated by quadrant analysis of CD3/CD4 or CD3/CD8 histograms. RESULTS: With the exception of CD3, where the range of values was quite narrow (10% variance), the correlation between the two methods was excellent (CD4: r = 0.98; CD8: r = 0.99; CD4/CD8: r = 0.96; p < 0.0001). CONCLUSION: Flow cytometry reveals similar results compared to immunocytochemistry in the determination of lymphocyte subsets characterised by CD3, CD4 and CD8 antigens.

[Fatal Aspergillus sepsis following orthotopic heart transplantation]. / Letale Aspergillus-Sepsis nach orthotoper Herztransplantation.

In a 64-year-old man heart transplantation had been performed for ischaemic heart disease. 7 months later severe vascular disease in the transplant necessitated a second transplantation. Both procedures had been performed under immunosuppression (cyclosporine, azathioprine, prednisolone, antithymocyte globulin), with a subsequent prednisolone maintenance dose of 10 mg daily. At first there were no complications, but 31 days after the re-transplantation atrial flutter developed. Although this was quickly terminated by drugs, circulatory failure set in. Because of signs of infection (white blood cell count 29,800/microliters, 17% stab cells, C-reactive protein 24 mg/l) broad-spectrum antibiotics were administered, but without response. As a trial anti-rejection treatment was started (prednisolone 250 mg daily: antithymocyte globulin 100 mg daily for 4 days). When cytomegalovirus (CMV) infection was demonstrated, ganciclovir and CMV hyperimmunoglobulin were administered and slow improvement was noted. The finding of Aspergillus in tracheal secretion was interpreted as apathogenic colonization. The patient died from cardiorespiratory failure 57 days after the second transplantation. Autopsy revealed Aspergillus sepsis.

Clinical significance of hyperbilirubinemia in patients with pulmonary hypertension undergoing heart-lung transplantation.

Hyperbilirubinemia is commonly observed in long-standing pulmonary hypertension and is thought to be the result of chronic right ventricular failure and subsequent liver congestion. To evaluate the clinical significance of preoperative hyperbilirubinemia, we reviewed the cases of 62 patients with pulmonary hypertension (31 primary and 31 Eisenmenger's syndrome) who underwent heart-lung transplantation between 1981 and 1990 at Stanford. Bilirubin levels higher than 1.0 mg/dl were noted in 58% of patients, and bilirubin levels higher than 2.0 mg/dl were noted in 23% of patients. Indirect hyperbilirubinemia accounted for 66% to 87% of the total bilirubin and tended to fluctuate with diuretic therapy. It was associated with polycythemia, reticulocytosis, and mild elevations of liver enzymes. Early postoperative mortality in patients with total bilirubin levels greater than 2.1 mg/dl, bilirubin levels greater than 1 mg/dl but less than 2.0 mg/dl, and levels less than 1 mg/dl was 58%, 27%, and 16%, respectively (p less than 0.05). In those with high bilirubin levels, four patients had severe hemorrhage as part of their terminal event. Cardiac cirrhosis was found at autopsy in 75% of the early deaths of patients with high bilirubin. We conclude that hyperbilirubinemia is a late manifestation of pulmonary hypertension. The mechanism of hyperbilirubinemia is probably the result of the combination of increased hemolysis and decreased uptake by the chronically congested liver. Patients with pulmonary hypertension and hyperbilirubinemia appear to be at greater surgical risk during heart-lung transplantation.