Activation of proinflammatory mediators in heart transplants from brain-dead donors: evidence from a model of chronic rat cardiac allograft rejection.
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Biomedical subjects
Publications and source records attributed to H H Scheld.
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Cyclosporine A (CsA) neurotoxicity is a common cause of seizures in transplant patients and others receiving immunosuppressive therapy. CsA at concentrations higher than the levels estimated for cerebrospinal fluid of the patients suffering from seizure attacks was ineffective to induce epileptiform field potentials (EFP) in in vitro brain-slice preparation. The aim of this study was to test the effect of CsA at lower concentrations on neuronal activity. Guinea-pig hippocampal slices were exposed to artificial cerebrospinal fluid containing CsA (0.1-2 microM). Furthermore, the effects of CsA (0.25-10 microM) were tested on EFP elicited by omission of Mg2+ from superfusate. Low concentrations of CsA (0.1-0.25 microM) induced EFP while higher doses (0.5-2 microM) failed to decrease the seizure threshold. CsA at concentrations of 0.25 and 1 microM had no significant effect on the low Mg2+-induced EFP. Higher CsA concentration (10 microM) strongly suppressed EFP. The results indicate that CsA at doses that are probably clinically relevant increases the neuronal excitability.
BACKGROUND AND OBJECTIVE: Myocardial ischaemia and infarction are major complications immediately after coronary artery bypass grafting. They may be due to incomplete surgical revascularization, perioperative anaesthetic management or vasospasm of arterial grafts, e.g. the internal mammary artery. Infusions of nifedipine or milrinone have been advocated to prevent spasm of the mammary artery. The study compared the incidence of myocardial ischaemia after continuous infusion of either nifedipine (0.2 microg kg(-1) min(-1)) or milrinone (0.375 microg kg(-1) min(-1)) in patients with compromised left ventricular function scheduled for elective coronary artery bypass graft. METHODS: After Institutional Review Board approval, this double-blinded randomized clinical study enrolled 30 adult patients with compromised left ventricular function (ejection fraction < 0.4) scheduled for elective coronary artery bypass grafting after written informed consent had been obtained. Ischaemia was detected by Holter electrocardiographic monitoring. The incidence of myocardial cell death was monitored by serial determinations of the creatine kinase-MB (CK-MB) and troponin-I. RESULTS: New ST elevation > or = 0.2 mV or new ST depression < or = 0.1 mV occurred in five of 15 patients in the milrinone group (33.3%) and in 13 of 15 patients (86.6%) in the nifedipine group (P < 0.05). There were increases in CK-MB and troponin-I in both groups. Twenty-four hours postoperatively, CK-MB (P = 0.003) and troponin-I (P = 0.001) were significantly higher in the nifedipine group. CONCLUSIONS: Perioperative continuous infusion of milrinone, compared with nifedipine, results in a significantly lower incidence of myocardial ischaemia and myocardial cell damage after elective coronary artery bypass grafting.
Abstract. In this communication, we will present a very rare case of the coexistence of non-Hodgkin's lymphoma (NHL; low malignant lymphocytic lymphoma of the B-cell type) and a non-small-cell lung carcinoma (NSCLC). A patient with a 15-year history of NHL developed a generalized relapse of the lymphoma with an additional tumor mass in the left lower lobe of the lung. Bronchoscopy showed the evidence of the NHL. Due to non-responding chemotherapy on the lung tumor, the coexistence of a second malignancy was histologically proved in a second bronchoscopy. Resection of the lung tumor with complex lobectomy and lymphadenectomy was performed. After that, chemotherapy with four cycles of carboplatin supplemented with taxol was induced. The patient was discharged from the hospital with a stable remission of both tumor diseases. Restaging after six months showed no evidence of a tumor relapse. This is a very rare case of the coexistence of NHL and NSCLC; we will discuss the difficulty of diagnostic and treatment of both tumor diseases.
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Surgical management is different for Jehovah's Witnesses than in customary operations. Preoperative measures primarily aim at an optimal hematological condition, whereas intraoperative activities are directed towards minimizing blood loss. However, physicians taking care of Jehovah's Witnesses are not only faced with the difficulties of adequate treatment, but also by psychological and legal issues. Since the German legal system does not offer clear-cut legislation with regard to the Jehovah's Witnesses transfusion issue, guidelines have been offered on how to encounter his issue.
BACKGROUND: Patients with severely impaired left-ventricular pump function who are eligible for heart transplantation increasingly undergo high-risk cardiac surgery due to the scarcity of donor organs. If these patients also qualify for long-term mechanical support, the latter can be used as back-up in case of postcardiotomy failure. METHODS: Since 1994, 36 patients (34 male, 2 female; mean age 51 +/- 7 years) underwent coronary bypass surgery/aneurysmectomy (n = 27), aortic valve replacement (n = 4), both (n = 1), or partial left ventriculectomy (n = 4) with a long-term mechanical assist device (Novacor, HeartMate, DeBakey) and were kept on stand-by with the device. Average left ventricular ejection fraction was 23 +/- 9 %, NYHA 2.9 +/- 0.5, and CCS 2.7 +/- 0.9. An intraaortic balloon pump was inserted prior to surgery in 13 patients. RESULTS: In 31 patients, high-risk surgery was performed, whereas 5 patients underwent immediate device placement as coronary revascularization was deemed impossible. 6 patients had postcardiotomy failure after coronary bypass surgery and were immediately provided with a long-term assist system. There were no significant differences in risk factors between the patient subsets. All conservatively operated patients survived and left the institution after 9.4 days and are currently at NYHA 1.5 +/- 0.5 or CCS 1.0 +/- 0, respectively. 6 of the 11 LVAD patients could be bridged to heart transplantation after 43 - 418 days, and 1 patient is still on support. CONCLUSION: High-risk conventional surgery with LVAD stand-by is feasible and seems to be a valuable alternative for heart-transplant candidates.
BACKGROUND: Gene therapy in cardiovascular disease promises to be of great impact. The ideal vector for the therapeutic gene transfection remains to be determined. The aim of the present study was to investigate the efficacy of gene transfer using adeno-associated virus vectors carrying the lacZ-reporter gene (AAV-lacZ) in a previously described coronary recirculation model. METHODS: Beating Lewis rat hearts perfused with oxygenated Krebs-Henseleit solution were harvested, after which an atrial septal defect (ASD) was created. All vessels were tied, and AAV-lacZ was injected into the aortic root. The solution was recirculated through the ASD to the left side of the heart and pumped back to the coronary arteries by the left ventricle. Incubation was allowed for 20 min at 15 degrees C, and the hearts were subsequently transplanted heterotopically in syngeneic rats. Three increasing doses (109, 1,010, 1,011 e. u.) of AAV-lacZ virus vectors were used to study the rate of gene transfer. All hearts were harvested after 7-60 days and evaluated histologically for expression of the lacZ-gene. RESULTS: Dose-dependent gene transfer was observed. Even after 60 days, there was no obvious decline in gene expression. CONCLUSION: Adeno-associated virus vectors offer effective and uniform gene transfer in the myocardium after transcoronary injection and recirculation. Due to the lack of immune response previously described, no decrease in gene expression can be observed up to 60 days after injection.
BACKGROUND: Mitral valve surgery for the correction of secondary mitral valve regurgitation (MR) in cardiomyopathy is associated with a poor outcome. Numerous studies have identified a severe left ventricular dysfunction as an indicator for a poor prognosis. The aim of the study was to asses the follow-up after mitral valve surgery and severe left ventricular dysfunction. METHODS: Between 1994 and 2000, 31 patients with mitral regurgitation and a left ventricular ejection fraction of below thirty percent undergoing isolated repair (n = 16) or replacement (n = 15) were investigated. All patients received maximal drug therapy. Twenty-one patients were New York Heart Association (NYHA) class III and 10 were class IV. Follow-up with echocardiography, ECG, and chest x-ray was performed in 87 % of the survivors. The mean duration of follow-up was 39 +/- 16 months. RESULTS: The mean duration of ICU and hospital stay was 3.6 +/- 2.1 days and 8.1 +/- 5.4 days, respectively. The 1-, 2-, and 5-year survival rates were 91 %, 84 %, and 77 %, respectively. NYHA class improved from 3.3 +/- 0.8 to 2.1 +/- 0.7 at follow-up (p < 0.01). The ejection fraction improved from 23.1 +/- 6.6 % to 36 +/- 6.8 % at follow-up (p < 0.02). Freedom from readmission for heart failure was 85 %, 79 %, and 68 % at 1-, 2-, and 5 years, respectively. CONCLUSIONS: Mitral valve surgery improves left ventricular function and reduces heart failure severity in patients with MR and cardiomyopathy. High-risk mitral valve surgery may be an alternative to heart transplantation in selected patients.
An 85-year-old patient suffered from progressive deterioration (NYHA III) for several months. Cardiac disease was suspected. Echocardiography as well as a CT scan of the heart revealed a heart tumor to be the cause. Tumor staging was negative. After transvenous biopsy, the diagnosis of a Burkitt lymphoma could be established. Due to the advanced age of the patient, the intended surgical therapy was turned down and the patient was treated with 6 courses of a potentially therapeutic chemotherapy (CHOP scheme), which was well tolerated by the patient. The following CT scan showed a complete remission of the tumor. Six months after chemotherapy the patient is in NYHA stage I.
BACKGROUND: The overall performance of available mechanical intravascular ultrasound catheters for fetal transesophageal echocardiography during fetoscopic fetal cardiac interventions in sheep has been limited by radioelectronic interference, low system frame rates, and low acoustic outputs. Therefore, a more reliable device is desired for human fetoscopic surgical procedures. METHODS AND RESULTS: We assessed the potential of a newly available 10-French phased-array intravascular ultrasound catheter for multimodal fetal transesophageal echocardiography in 5 fetal sheep between 78 and 98 days of gestation (term, 145 to 150 d). The intravascular ultrasound catheter was easily inserted through the mouth into the esophagus in all 5 sheep fetuses (mean weight, 600 g), and it permitted high-quality 2D imaging of the fetal heart in vertical imaging planes that were validated by MRI. Color Doppler and pulsed Doppler imaging permitted clear assessment of fetal cardiovascular flows and recording of velocity-time integral tracings of the fetal heart and great vessels. The vertical imaging planes were particularly useful to demonstrate interventional material inside the fetal heart and great vessels. CONCLUSIONS: Our early experience with the phased-array intravascular ultrasound catheter indicates that multimodal fetal transesophageal echocardiography has now become possible in these smallest of patients.
There is an ongoing debate whether female gender is associated with increased cardiovascular morbidity and mortality, especially after coronary interventions. The impact of gender on the outcome of patients undergoing emergency coronary artery bypass grafting (CABG) for failed PTCA was analyzed. Clinical and procedural data of all patients who underwent PTCA and subsequent emergency CABG at our institution from 1989 to 1998 were assessed. During these 10 years, 6681 PTCA procedures were performed, 1312 in women (19.6%). Subsequently, 110 patients underwent emergency CABG of whom 32 were females (29.1%). Postoperatively, 9 women and 5 men died (mortality 12.7%). Women presented with higher age (61.2 +/- 2.1 vs. 58.3 +/- 1.0 years, n.s.), smaller height (1.61 +/- 0.01 vs. 1.76 +/- 0.01 m, p < 0.0001), lower weight (67.7 +/- 2.4 vs. 82.1 +/- 1.2 kg, p < 0.0001), smaller body surface area (1.70 +/- 0.04 vs. 1.98 +/- 0.02 m2, p < 0.0001), and higher comorbidity as expressed by their Cleveland score (7.9 +/- 0.3 vs. 7.1 +/- 0.2, p = 0.013). The risk for failure of PTCA with subsequent emergency CABG was higher in women than in men (2.4% vs. 1.5%, p = 0.012, odds ratio 1.66) as well as for postoperative death (28.1% vs. 6.4%, p = 0.004, odds ratio 4.39). Women had longer in-hospital stays (19.7 +/- 4.2 vs. 12.9 +/- 1.3 days, p = 0.044). Logistic regression analyses found lower weight (p = 0.003), higher number of diseased coronary vessels (p = 0.024) and higher Cleveland score (p = 0.023) to be independent predictors of operative mortality. A Kaplan-Meier model (follow-up 5.3 +/- 2.5 years) showed an increased in-hospital mortality in women (p = 0.0034, log rang test), but a comparable long-term survival. Women had an increased risk for failure of PTCA and a markedly higher operative mortality after emergency CABG. In multivariate analyses, however, gender was not an independent predictor of postoperative death.
BACKGROUND: To predict the outcome after myocardial revascularisation, a clear separation between hibernation and/or repetitive stunning on the one hand and myocardial scarring on the other hand is of importance. METHODS AND RESULTS: A total of 44 patients was included in this study. In 35 patients with chronic myocardial ischaemia and an indication for coronary bypass-surgery, epicardial mapping of local activation was performed. Nine patients with LV aneurysm and an indication for antitachycardia surgery were also included. For simultaneous recording of the local electrograms during sinus rhythm, a sock electrode with 102 bipolar leads was used. The regional myocardial contraction pattern was assessed from preoperative angiograms and regional myocardial metabolism (viability) from 18F-FDG PET, respectively. The results were projected on the grid of the intraoperative position of the sock electrode. This enabled regional comparison of electrogram characteristics to local contraction patterns and viability. For the characterisation of local electrograms, peak-to-peak amplitude and duration of activation were calculated using custom-made automated computer-algorithms. Dysfunctional but viable areas showed normal or almost normal electrographic signal characteristics. In contrast, dysfunctional and non-viable myocardium showed a distinct reduction of local amplitudes and prolongation of signal duration. These changes were even more intense in areas of LV aneurysms. CONCLUSIONS: In patients with chronic ischaemic myocardium, a mismatch between mechanical function and local electrogram characteristics was observed in areas with preserved metabolism. Thus, normal epicardial electrograms in regions of myocardial dysfunction may be an indicator for myocardial viability.
A 68-year-old male patient developed pyoderma gangrenosum after elective aortic valve replacement. Treatment with steroids and clofazimine was initiated, which resulted in rapid cessation of the necrotic process. Due to thoracic instability, stabilization of the sternum was performed followed by surgical debridement and atraumatic wound closure. Postoperatively, immunosuppression with cyclosporine A was added; the patient recovered completely. Pyoderma gangrenosum is a potential life-threatening complication that must be considered in patients with severely impaired wound healing after cardiac operation.
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BACKGROUND: Acute nonocclusive mesenteric ischemia (NOMI) is a rare but often fatal event after cardiac surgery. METHODS: Twenty patients with ongoing ileus after cardiac surgery despite maximal laxative treatment underwent selective mesenteric angiography. In cases of pathological radiographic findings, papaverine was continuously administered via an intraarterial perfusion catheter. RESULTS: Severe NOMI was confirmed in seven patients (mean lactate: 6.9 +/- 8.3 mg/dL), mild to moderate findings in another seven (mean lactate: 1.4 +/- 1.1 mg/dL). One patient had thromboembolic occlusion of the superior mesenteric artery; five patients demonstrated normal imaging findings. In nine of fourteen patients (64%) treated with papaverine, symptoms improved within hours (defecation occurred after 4-29 hours, mean 13 +/- 8.1 hours). No side effects or complications occurred in connection with the papaverine treatment. The clinical condition of five patients deteriorated. Four patients underwent laparotomy with creation of an ileostomy or colostomy, two of whom presented with severe intestinal ischemia and later died. One patient died prior to laparotomy. CONCLUSIONS: Selective mesenteric angiography with continuous papaverine administration is a simple, fast, and effective diagnostic and therapeutic tool to reduce the need for laparotomy for symptoms of ileus after open-heart surgery.
A continuing increase in the number of very elderly patients with symptomatic heart disease referred for cardiac surgery has been observed in the past. Since 1990 all patients of 80 years and above have been included in a prospective study. We report on the results of the first 200 consecutive patients (mean age: 82.2+/-2.1 years). Operative procedures ranged from isolated myocardial revascularization and valve replacement to very complex operations. In a majority of patients, the operations had to be performed as urgent or emergency cases because of advanced heart disease. Overall 30 day mortality was 9.5%. More than two thirds of patients needed treatment of perioperative complications. During long-term follow-up, cardiac surgery in octogenarians has proved to be very effective with excellent functional status and quality of life. Because of favorable results elderly patients should not be denied the benefits of cardiac surgery requiring utilization of significant medical resources.