PubMed Health⌕ Search

Biomedical subjects

F U Sack

Publications and source records attributed to F U Sack.

At least 19 recordsLinked to original sources
PubMed2006

Cyclosporine withdrawal improves renal function in heart transplant patients on reduced-dose cyclosporine therapy.

Renal failure is a major cause of morbidity after heart transplantation. It is unclear whether calcineurin inhibitor (CNI) free immunosuppression provides more nephroprotection than low-dose CNI therapy. Thirty-nine patients with renal failure on low-dose cyclosporine A (CsA) were studied (62.9 +/- 8.7 years, five female, 8.2 +/- 4.3 years posttransplant, serum creatinine: 1.9 +/- 0.3 mg/dL, calculated GFR (cGFR): 48.2 +/- 18.3 mL/min, CsA C0 level: 64.0 +/- 19.9 ng/mL). All patients had been treated with low-dose CsA >6 months, renal function was stable or slowly decreasing (creatinine 1.7-3.5 mg/dL). Nineteen patients were randomized to discontinuation of CsA and overlapping rapamycin therapy initiation (RAPA), 20 patients continued low-dose CsA (control). Three patients (16%) discontinued rapamycin medication for side effects (diarrhea, skin rash), two patients developed pneumonia and pulmonary embolism, respectively, no rejection or other infectious complications were seen. After 6 months, renal function in the control group was unchanged. In the RAPA group, renal function markedly improved (creatinine: 2.08 +/- 0.15 to 1.67 +/- 0.13 mg/dL, cGFR: 48.5 +/- 21.4 to 61.7 +/- 21.4 mL/min (p < 0.001 within and between groups)). In carefully selected late survivors following heart transplantation who are at low risk of rejection, CNI-free rapamycin-based immunosuppression improves cGFR even in those already receiving low-dose CsA therapy. The results of this study warrant further confirmation in larger clinical trials that are powered to assess clinical outcomes.

Adult↗
PubMed2006

The Eurotransplant High-Urgency Heart Transplantation Program: an option for patients in acute heart failure?

OBJECTIVE: The Eurotransplant High-Urgency (HU) Heart Transplantation Program allows urgent heart transplants to be carried out in rapidly deteriorating patients with acute-to-chronic heart failure on the elective waiting list. But do the results of HU heart transplantation justify performing primary heart transplantation in these critically ill patients and offer an acceptable outcome? METHODS: Between 2000 and 2004, 64 heart transplantations (HTx) (32 elective and 32 HU-HTx) were performed in our department. After having been accepted in an auditing process based on HU criteria, intensive care patients in NYHA functional class IV (cardiac index 1.7 l/min/qm BS), in end-organ failure (creatinine 1.5 mg/dl), and with catecholamine dependence (dobutamine 8 microg/kg/min), are given priority with respect to organ allocation, and their data were compared to data from elective patients from the same period. RESULTS: HU requests were accepted in 97 % of cases. Two requests were not accepted, and both patients with contraindications for assist device implantation died within one week. The HU patients were 100 % in NYHA class IV, 93 % of the elective patients were in NYHA class III. Waiting time on the HU list was 13 days, and 7 of these patients died before HTx. Following heart transplantation, survival rates at 30 days and at one year of the HU group were 88 % and 85 % versus 94 % and 93 % in the elective group. CONCLUSIONS: This study shows that end-stage heart failure patients in the HU program can be transplanted primarily with good results if an organ is available in time. We are still in the position where the HU program only manages the organ shortage; there are still too many patients on the waiting list who die before receiving a donor organ.

Acute Disease↗
PubMed2002

Dopexamine attenuates microvascular perfusion injury of the small bowel in pigs induced by extracorporeal circulation.

BACKGROUND: Cardio-thoracic surgery with the use of extracorporeal circulation may lead to an impairment of splanchnic perfusion. The aim of this study was to investigate the effect of dopexamine on gastrointestinal microvascular perfusion failure due to extracorporeal circulation. METHODS: Twenty landrace pigs served as laboratory animals. A loop of the terminal ileum was exteriorized for microscopic observation. In 13 animals a partial left-heart bypass (pLHB), with a non-pulsatile pump flow of approximately 50% of the cardiac output, was established for 2 h. Seven animals received a continuous i.v. infusion of 3 micrograms kg-1 min-1 dopexamine from the beginning of pLHB to the end of the experiment. Seven sham-operated animals served as controls. The microcirculatory network was analysed by means of intra-vital microscopy prior to, during pLHB, and 2 h after bypass. RESULTS: Despite normal haemodynamics measured by arterial pressure and cardiac output, pLHB led to significant impairment of microvascular perfusion characterized by arteriolar vasoconstriction, reduction of functional capillary density (FCD) to 30% 2 h after weaning off bypass and diminished blood-cell velocities in submucous venules. Dopexamine attenuated this perfusion impairment, preventing arteriolar vasoconstriction. FCD remained normal. CONCLUSION: Our data demonstrate that treatment with the vasoactive drug dopexamine leads to a significant reduction of the perfusion injury of the small bowel.

Adrenergic beta-Agonists↗
PubMed2001

Influence of steroids on microvascular perfusion injury of the bowel induced by extracorporeal circulation.

BACKGROUND: Extracorporeal circulation is associated with gastrointestinal complications. By means of intravital microscopic methods, we investigated whether preoperative treatment with steroids can attenuate the impairment of the bowel microcirculation. METHODS: In 20 pigs, a partial left heart bypass (pLHB) was established. A loop of the terminal ileum was exteriorized for intravital-microscopic observation. Seven sham-operated animals served as controls. In 13 animals, pLHB was established for 2 hours with a flow rate of 2,000 mL per minute; 7 of the animals received 20 mg/kg body weight prednisolone preoperatively. The microcirculatory network was analyzed before, during pLHB, and 2 hours after bypass. RESULTS: Despite unchanged macro-hemodynamics, pLHB resulted in a significant microvascular perfusion injury of the small bowel. Arteriolar vasoconstriction and a reduction of perfused capillaries per unit area (functional capillary density) to 30% of prebypass values could be found. Blood cell velocities were reduced in submucuous collecting venules. In the steroid-treated animals, the functional capillary density remained normal. In addition, arteriolar vasoconstriction could be prevented. CONCLUSIONS: Treatment with prednisolone largely prevents the microcirculatory alterations in the small bowel induced by extracorporeal circulation.

Animals↗
PubMed2001

Capillary endothelia and cardiomyocytes differ in vulnerability to ischemia/reperfusion during clinical heart transplantation.

OBJECTIVE: The development of accelerated graft arteriosclerosis is a major cause of late death after orthotopic heart transplantation. The influence and the extent of peritransplant injury, especially of cardiomyocyte or capillary endothelial cell edema is discussed. METHODS: A morphometric ultrastructural analysis of myocardial biopsies from 29 donor hearts (21 male, age 34+/-11 years) was performed. Right ventricular biopsies were obtained before cardioplegia (A), immediately following cardioplegia (B) (Custodiol, Dr. F. Köhler Chemie GmbH, Alsbach-Hähnlein, Germany), before implantation (C), after 30 (D) or 60 (E) min of reperfusion and 1 week after transplantation (F). Mean ischemic time was 185+/-68 min. Quantitative electron microscopy was carried out in five samples per heart and time point and in 30 test fields per sample by 'random systematic sampling' and 'point and intersection counting'. As parameters for cell edema the volume density of myofibrils in cardiomyocytes and the mean barrier thickness of capillary endothelia were analyzed. P-values of less than 0.05 were regarded as significant. Significant differences in contrast to the previous values are marked by *. RESULTS: The volume density of myofibrils (vol.%) was as follows: (B) 63.6+/-3.2, (C) 61.8+/-3.2, (D) 62.9+/-3.2, (E) 63.6+/-4.5. The mean barrier thickness (nm) was as follows: (A) 353+/-21, (B) 376+/-59, (C) 416+/-71*, (D) 473+/-45*; (E) 453+/-50*, (F) 379+/-39. CONCLUSIONS: Apart from a generally accepted edema of cardiomyocytes a relevant capillary endothelial cell edema develops during clinical heart transplantation. In contrast to cardiomyocytes the cell edema of endothelia shows a more pronounced and significant progression during cold ischemia and early reperfusion. After 60 min of reperfusion it is still significantly more pronounced than at the onset of ischemia. After 1 week there are no statistical differences compared to the initial values. Thus, an edema of capillary endothelia probably will trigger inhomogeneities in capillary perfusion. Peritransplant injury of endothelia may contribute to the later development of accelerated allograft arteriosclerosis.

Adult↗
PubMed2001

A novel perfusion catheter for hybrid procedures in minimally invasive bypass surgery.

BACKGROUND: Combined off-pump bypass grafting and percutaneous coronary intervention (hybrid procedures) is supposed to be beneficial for high-risk patients. We developed a novel perfusion catheter to facilitate these hybrid interventions. METHODS: First, we tested coagulatory activation in vitro. Afterwards, 6 landrace pigs underwent active coronary perfusion of the LAD. In a second study, 15 pigs underwent off-pump bypass surgery (LIMA to LAD grafting) and the catheter was used to provide myocardial perfusion and prevent bleeding at the site of the coronary anastomosis. RESULTS: In the in vitro perfusion studies, no activation of coagulation or clotting occurred. Active coronary perfusion was feasible without signs of regional myocardial ischemia or coagulation over a 50-minute period. During off-pump bypass surgery, the catheter prevented bleeding in the operation field and facilitated the surgical procedure. CONCLUSION: The new perfusion catheter can optimize the conditions of off-pump bypass surgery by preventing bleeding in the operation field, maintaining myocardial perfusion and allowing direct angiographic control of the anastomosis. Therefore, this new technique could be an important tool to facilitate hybrid interventions.

Anastomosis, Surgical↗
PubMed1999

Vaccination against tick-borne encephalitis under therapeutic immunosuppression. Reduced efficacy in heart transplant recipients.

Patients after organ transplantation are at an increased risk of microbial infections and might benefit from active vaccination. Due to therapeutic immunosuppression the efficacy of immunizations is, however, reduced and difficult to predict. Efficacy of vaccination against tick-borne encephalitis (TBE) using an abbreviated immunization schedule was compared in 31 heart transplant recipients (age: 54.5 +/- 11.5 years, mean time after transplantation: 53.5 +/- 23.7 months) under cyclosporine-based immunosuppression and 29 controls. TBE vaccination was well tolerated by the transplant recipients; spectrum and frequency of adverse events were similar to controls. In the transplant patients, seroconversion rate (35% versus 100%; p < 0.001) and the geometric mean of post-vaccinal antibody titres (0.98 (SF: 2.3) U/ml versus 5.46 (2.2) U/ml; p < 0.001) were markedly reduced in comparison to the control group. No clinical or demographic predictors of vaccination success could be established in the transplant patients. Due to the limited efficacy, TBE vaccination cannot be recommended as a routine procedure in heart transplant recipients at risk of TBE virus infection. TBE vaccination may be performed safely in selected cases, but repeated titre controls to confirm vaccination success would be required.

Adult↗
PubMed1998

Circulating interleukin-1 receptor antagonist (IL-1RA) serum levels in patients undergoing orthotopic heart transplantation.

In a pilot study we determined the serum levels of circulating interleukin-1 receptor antagonist (IL-1ra) in patients undergoing orthotopic heart transplantation and in control patients scheduled for open heart surgery without allograft transplantation. Blood samples were obtained from 12 transplant recipients and 7 controls prior to the operative procedures to determine baseline values. Serum levels of IL-1ra were measured within 12 h of decrossclamping of the aorta and every 24 h for the following 14 days. Endomyocardial biopsies were obtained weekly for the 1st month after transplantation. Compared to baseline values, IL-1ra serum levels 12 h after decrossclamping of the aorta were significantly higher both in the control group (507 +/- 165 vs 3980 +/- 452 pg/ml, P < 0.01) and among the transplant recipients (413 +/- 180 vs 4117 +/- 459 pg/ml, P < 0.01) IL-1ra levels remained significantly elevated for 2 and 5 days, respectively. There were no significant differences in the IL-1ra serum levels between the two groups throughout the observation period. Endomyocardial biopsies of two patients showed acute allograft rejection, Billingham grade IIIa and IIIb, respectively. In both cases, the rejection episodes were accompanied by a renewed and more pronounced elevation in the IL-1ra serum levels beyond 4000 pg/ml for at least 2 days. These preliminary results indicate that IL-1ra may be a nonspecific immune marker during the first few days after orthotopic heart transplantation and cardiopulmonary bypass. Moreover, renewed, prolonged increases in IL-1ra appear to be associated with rejection. Further studies are needed to confirm the predictive value of IL-1ra in the detection of acute allograft rejection.

Biomarkers↗
PubMed1998

Elevated serum concentrations of cardiac troponin T in acute allograft rejection after human heart transplantation.

OBJECTIVES: This study evaluates the concept and diagnostic efficacy of using serum troponin T for the detection of cardiac graft rejection. BACKGROUND: Cardiac troponin T is a cardiospecific myofibrillar protein, which is only detectable in the circulation after cardiac myocyte damage. It might be expected to be released during acute heart allograft rejection, allowing noninvasive rejection diagnosis. METHODS: In 35 control subjects and in 422 samples from 95 clinically unremarkable heart allograft recipients more than 3 months postoperatively, troponin T serum concentrations were compared to the histological grade of acute graft rejection in concurrent endomyocardial biopsies. RESULTS: Mean troponin T serum concentrations were identical in control subjects (23.2 +/- 1.4 ng/liter) and in heart transplant recipients without graft rejection (International Society for Heart and Lung Transplantation [ISHLT] grade 0; 22.4 +/- 1.7 ng/liter). Mean troponin T concentrations increased in parallel with the severity of graft rejection (ISHLT grade 1: 27.8 +/- 1.8 ng/liter; grade 2: 33.2 +/- 2.7 ng/liter; grade 3A: 54.6 +/- 6.5 ng/liter; grade 3B and 4: 105.4 +/- 53.7 ng/liter; p < 0.001 for grades 3 and 4 vs. grades 0 and 1). The proportion of positive samples also increased in parallel with rejection severity, reaching 100% in rejections of grade 3B and 4. Sensitivity and specificity for the detection of significant graft rejection (ISHLT grade 3/4) were 80.4% and 61.8%, respectively. The negative predictive value was most remarkable with 96.2%. Intraindividual longitudinal analysis of troponin T levels and biopsy results in 15 patients during long-term follow-up confirmed these findings. CONCLUSIONS: The present data demonstrate that acute allograft rejection after human heart transplantation is often associated with increased serum concentrations of troponin T. All cases of serious forms of graft rejection would have been detected before the development of clinical symptoms. Measurement of troponin T levels may become a useful ancillary parameter for noninvasive rejection diagnosis, being most valuable in the exclusion of severe cardiac graft rejection.

Acute Disease↗
PubMed1997

Transferral of extrathoracic donor neoplasm by the cardiac allograft.

The transference of neoplasm from the donor to the recipient is a rare but recognized complication of organ transplantation. It has been reported after kidney transplantation from cadaver donors. We report a case in which an extrathoracic tumor was transmitted by the donor heart. The donor heart was harvested from a 46-year-old local donor and immediately transplanted to a 62-year-old female recipient. While implantation was performed, a hypernephroma was detected in the multiorgan donor. The ongoing heart transplantation could not be stopped. Four weeks after operation, the patient was discharged from the hospital. During the first year after transplantation, the clinical course was uneventful. One year after operation, the patient was admitted to the hospital with symptoms of weakness and fever. A right facial hemiparesis occurred, and a soft tumor was palpable subcutaneously in the right supraorbital region. Histologic examination revealed a malignant tumor with characteristics identical to the donor hypernephroma. In spite of chemotherapy and radiation therapy, dramatic tumor progression occurred with multiorgan metastases, which led to the death of the patient 2 months after admission.

Brain Neoplasms↗
PubMed1995

Treatment of dilated cardiomyopathy with dynamic cardiomyoplasty: the Heidelberg experience.

BACKGROUND: Data concerning the efficacy of dynamic cardiomyoplasty are still inconsistent, especially in terms of improvement of left ventricular function. METHODS: Between August 1990 and February 1994, eight isolated cardiomyoplasty procedures were performed in patients with cardiomyopathy (ejection fraction, 0.14 to 0.32; New York Heart Association class III) and contraindications to heart transplantation. RESULTS: Follow-up was 41.1 +/- 14.1 months. One patient died 2 months and another 3 years after operation. Considerable symptomatic improvement was found in 6 of 7 patients, 3 of whom went back to work. One patient with severe pulmonary hypertension exhibited no improvement. Mean New York Heart Association-class decreased from 3.0 to 1.9 (p < 0.001). Echocardiography showed an increase in fractional shortening and in peak aortic flow velocity in all patients. Left ventricular ejection fraction increased from 0.21 +/- 0.05 to 0.38 +/- 0.16 (n = 7, p < 0.015) at 1 year, to 0.37 +/- 0.18 (n = 6, p < 0.05) at 2 years, and to 0.36 +/- 0.19 (n = 5, not significant) at 3 years. Pulmonary artery pressure tended to decrease over time. No significant change in exercise level or maximal oxygen consumption during treadmill testing was observed. CONCLUSIONS: Our preliminary results show that patients may exhibit an impressive clinical improvement after cardiomyoplasty, with only moderate changes in objective hemodynamic indices. We do not consider cardiomyoplasty an alternative to heart transplantation, but reserve it for patients with contraindications to heart transplantation.

Cardiomyopathy, Dilated↗
PubMed1995

Dynamic cardiomyoplasty: indication, surgical technique, and results.

The efficacy of dynamic cardiomyoplasty is still controversial. To date more than 400 patients have been operated worldwide. In recent years the indication and the surgical technique have become more uniform, which makes results from different centers eligible for comparison. We performed cardiomyoplasty exclusively in patients with contraindications for heart transplantation, such as chronic and recurrent infections or severe, irreversible sequelae of diabetes. Between August 1990 and October 1994, 8 isolated cardiomyoplasty procedures were performed in patients with cardiomyopathy (EF 14-32%, all in NYHA III). One patient died 2 months after surgery. Reported are the results of 7 patients after a mean follow-up of 41.1 +/- 14.1 months. Considerable symptomatic improvement was found in 6 or 7 patients, 3 of whom went back to work. One patient with severe pulmonary hypertension exhibited no improvement. In the others NYHA class improved by at least one. Echocardiography showed an increase in fractional shortening in all patients. LVEF increased from 21.2 +/- 5.2% to 38.1 +/- 15.9% (n = 7, p < 0.015) at 1 year, to 36.6 +/- 17.6% (n = 6, p < 0.05) at two years, and to 36.4 +/- 18.9% (n = 5, NS) at three years. Pulmonary artery pressure tended to decrease at rest over time. Resting lung function showed no change of vital capacity and FEV1. No significant change in exercise level and maximal O2-consumption during treadmill testing was observed. One patient died 34 months after the operation from sudden death. Our preliminary results show that patients after cardiomyoplasty may exhibit an impressive clinical improvement with less striking changes of objective hemodynamic parameters. This data is in agreement with the results of all other investigators. Some possible mechanisms of action are discussed and a risk profile suggested. According to the current state of experience with cardiomyoplasty, we do not consider this method an alternative to heart transplantation, but reserve it for patients with contraindications for heart transplantation.

Cardiomyopathies↗
PubMed1994

[Atrioventricular valve insufficiency and atrial geometry in orthotopic heart transplantation].

Tricuspid and mitral valve regurgitation are commonly observed in patients after orthotopic cardiac transplantation (HTX). The etiology is still controversial. Aim of the present study was to assess the degree of regurgitation and its etiology. Twenty-five patients (mean age 47.9 +/- 11.8 years) undergoing HTX were studied intraoperatively by transesophageal echocardiography. The degree of tricuspid and mitral valve regurgitation was assessed by planimetry of maximum systolic area of the regurgitant jet (JA). The cross-sectional area of right and left atrium and the recipient (R) and the donor (D) cross-sectional area of the atria, and their ratio (R/D) were assessed by two-dimensional echocardiography. The following preoperative and perioperative hemodynamic parameters were measured: systemic arterial pressure, cardiac index, pulmonary artery pressure, and pulmonary vascular resistance. Tricuspid regurgitation was found in 21/25 (84%) patients, mitral regurgitation in 12/25 (48%). The degree of mitral regurgitation showed no correlation to any of the studied parameters. Tricuspid regurgitation showed no correlation to the hemodynamic parameters, but showed significant correlation to R/D ratio (JA versus R/D: r = 0.90; SEE = 0.2) and to the dimensions of the recipient atrium (JA versus R: r = 0.89; SEE = 1.9). Three patients who underwent bicaval anastomoses did not show tricuspid regurgitation. In conclusion, tricuspid regurgitation has a higher prevalence than mitral regurgitation and occurs in most patients immediately after HTX; mitral regurgitation was less frequent than tricuspid regurgitation and was not correlated to the hemodynamic parameters or to the distortion of atrial geometry; tricuspid regurgitation was significantly correlated to the ratio of recipient/donor right atrium; surgical techniques reducing the recipient atrium may decrease the occurrence and the degree of tricuspid regurgitation.

Adult↗
PubMed1992

Superiority of endocardial versus epicardial implantation of the implantable cardioverter defibrillator (ICD).

The implantable cardioverter-defibrillator (ICD) has proved to be an efficient device for the treatment of severe ventricular tachyarrhythmias (VT). From May 1985 to August 1991, the ICD was implanted in 107 patients of whom 72% suffered from coronary artery disease, 17% from cardiomyopathy, 5% from long QT-syndrome and 6% from other heart disease. All patients had a life threatening episode of VT or at least one episode of ventricular fibrillation. Of 107 implants, 12% were combined with other heart surgery, 55% were isolated epicardial implantations (epi I) and in 33%, the novel endocardial (endo I) approach was chosen. Between epi I and endo I we found no difference in operation time, but time for ICU and in-hospital stay was significantly shorter using the transvenous approach. In addition, sensing and pacing capability of the endocardial screw-in electrode was superior and the need for thoracotomy was avoided, a particular advantage in patients with previous heart surgery. Complications after epi I were: temporary low cardiac output, 1; perioperative death, 2; infection, 3, and after endo I: electrode dislocation, 2. Hence, endo I may become the method of choice for patients without concomitant surgery.

Adult↗