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Biomedical subjects

M Grimm

Publications and source records attributed to M Grimm.

At least 19 recordsLinked to original sources
PubMed1997

Prostaglandin E1--bridge to cardiac transplantation. Technique, dosage, results.

BACKGROUND: Heart transplantation candidates who remain severely symptomatic despite therapy are normally hospitalized. Continuous infusion of intravenous drugs from a portable pump may allow such patients to live a fairly active life until a donor heart is found. AIM: To investigate in an open pilot study if heart transplantation can be safely accomplished if these patients are continuously bridged with various regimens including inotropic support with low-dose dobutamine in conjunction with dopamine and prostaglandin E1. METHODS: We report on 5 years' experience with prostaglandin E1, a potent vasodilator with proven efficacy in severe heart failure when coupled with catecholamines. From 1990 to 1995 54 heart transplantation candidates were bridged with prostaglandin E1 in addition to dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 (group A; n = 32) or in addition to 3 micrograms.kg-1 min-1 dopamine alone (group B; n = 22), and 11 heart transplantation candidates were bridged with dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 only (group C; n = 11). In an initial dose-ranging test, prostaglandin E1 was uptitrated to side effect limit (29 +/- 1 ng.kg-1.min-1). Haemodynamics, except for stroke volume index, were similar in all patients at baseline and a sufficient haemodynamic response (20% increase in stroke volume) was observed during the acute study. Fifty percent of the peak dose was used for initiating chronic therapy; the dose of prostaglandin E1 was further reduced if side effects recurred. RESULTS: Twenty-nine (54%) patients in groups A and B and six in group C could be discharged home with chronic therapy via a Hickman catheter connected to a portable pump. After 4 weeks in six patients in group A and in 13 patients in group B, when prostaglandin E1 had been reduced from 15 +/- 2 ng.kg-1.min-1 to 8 +/- 1 ng.kg-1 min-1 increases in cardiac index and decreases in systemic vascular resistance were sustained, and a permanent decrease in pulmonary vascular resistance index was observed in group B. Intravenous therapy was changed in nine patients (3/1/5) because of side effects and worsening heart failure. Prostaglandin E1 was withdrawn in three of these patients because of an increase in serum creatinine (3 mg.100 ml-1), and in one because of noncompliance. In total, there were 17 cardiac deaths (9/6/2), 42 heart transplants (22/14/6) and six (1/2/3) weaned survivors (including one non-cardiac death) in this study. Overall outcome was similar in groups A and B, but distribution after 2 months appeared to be different (P < 0.05) based on more transplantations in group A. CONCLUSION: We concluded that chronic infusions with prostaglandin E1 at reduced dosages is a feasible and safe therapeutic adjunct to bridge end-stage heart failure patients and may yield desirable effects in a subset of patients in the absence of inotropic support by dobutamine.

Alprostadil↗
PubMed1996

Cyclosporine may affect improvement of cognitive brain function after successful cardiac transplantation.

BACKGROUND: The effects of cardiac transplantation on cognitive brain function are uncertain. METHODS AND RESULTS: We measured cognitive brain function and quality of life in out-of-hospital cardiac transplant candidates (n = 55; ejection fraction, 19.9%; age, 54.8 years [means]). After transplantation, the patients were serially reevaluated at 4 months (n = 25) and at 12 months (n = 19). Brain function was measured objectively by cognitive P300 evoked potentials. Additionally, standard psychometric tests (Trail Making Test A, Mini-Mental State Examination, and Profile of Mood State test) were performed. Cognitive P300 evoked potentials were impaired in cardiac transplant candidates (359 ms, recorded at vertex) compared with 55 age- and sex-matched healthy subjects (345 ms, P < .01). Trail Making Test A was also abnormal (45 versus 31 seconds in 55 healthy subjects, P < .01). After transplantation, P300 measures were normalized at 4 months (345 ms, P < .05 versus before transplantation) but declined again at 12 months (352 ms, P = NS versus before transplantation). Stepwise multiple regression analysis revealed that cumulative cyclosporine dosage was the only predictor of individual cognitive brain function 4 months (753 mg/kg body wt, P < .05) and 12 months (2006 mg/kg body wt, P < .01) after transplantation, respectively. CONCLUSIONS: Objective cognitive P300 auditory evoked potential measurements indicate that cognitive brain function is significantly impaired in patients suffering from stable end-stage heart failure. Successful cardiac transplantation is effective to fully normalize impaired brain function. Subsequent relative long-term decline of cognitive brain function after successful cardiac transplantation is strongly suggested to be related to cumulative cyclosporine neurotoxicity.

Affect↗
PubMed1996

Decrease in pacemaker incidence after orthotopic heart transplantation.

A decrease in sinus node dysfunction and pacemaker requirement after orthotopic heart transplantation was observed over a 6.5-year period, probably indicating the effect of a learning curve. Indirect evidence suggests a traumatic genesis of sinus node dysfunction after cardiac transplantation.

Arrhythmia, Sinus↗
PubMed1996

Nutritional status, ICU duration and ICU mortality in lung transplant recipients.

OBJECTIVE: To determine the relation of malnutrition and underlying diagnosis to the length of stay in the Intensive Care Unit (ICU) and to mortality after lung transplantation (LTX). DESIGN: Retrospective ICU chart review. SETTING: Cardiothoracic ICU in a University hospital. PATIENTS: Fifty-one consecutive patients who suffered from end-stage lung disease from April 1992 to January 1994. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The median time spent in the ICU was 5 days (range, 2-123 days). Patients with an underlying diagnosis of obstructive lung disease had significantly shorter ICU stays (median 4 days; range, 2-28 days) than those with restrictive lung disease (median 7 days; range, 2-123 days) (p = 0.005) or pulmonary hypertension (median 10 days' range, 2-38 days) (p = 0.041). Significant differences in ICU duration were observed between patients after double lung transplantation (median 10 days; range, 2-123 days) and those after single lung transplantation (median 4 days; range, 2-36 days) (p = 0.004). No statistically significant difference in ICU duration was found between patients with different nutritional statuses. In those patients who could not be discharged from the ICU before the 5th day, a body mass index (BMI) below the 25th percentile was a statistically significant risk factor for ICU mortality (p = 0.05). CONCLUSIONS: We conclude that the type of transplant procedure and the underlying diagnosis are important predictive indicators of ICU duration. A poor nutritional status (BMI below the 25th percentile) is a risk factor for ICU mortality in cases of patients who stay for 5 days or longer in the ICU.

Adolescent↗
PubMed1996

Impact of glutaraldehyde on calcification of pericardial bioprosthetic heart valve material.

BACKGROUND: This study was conducted to investigate the impact of the preservation method of bioprosthetic heart valve materials on calcification rates and biocompatibility of the biologic tissue. METHODS: In subcutaneous rat implants, conventionally preserved bioprosthetic heart valve material was compared with bovine pericardium that was treated with L-glutamic acid to reduce residual glutaraldehyde released from the fixed tissue. Both these methods were compared with bovine pericardium that was stabilized by a dye-mediated photooxidation reaction without glutaraldehyde. Biocompatibility of these biomaterials was tested in vitro using human endothelial cell cultures. RESULTS: Conventionally preserved bovine pericardium with a high amount of glutaraldehyde incorporated into the tissue resulted in severe calcification 63 days after subcutaneous implantation in rats (165.4 +/- 20 mg Ca2+/g dry weight). Postfixation treatment with L-glutamic acid, which reduces free, unbound aldehyde groups, showed a significant decrease in calcification (89.6 +/- 14 mg Ca2+/g dry weight). Glutaraldehyde-free preservation by dye-mediated photooxidation showed no calcification after 63 days of subcutaneous implantation (1.0 +/- 0.4 mg Ca2+/g dry weight). Regular endothelial cell proliferation was observed on photooxidized and L-glutamic acid-treated tissue, whereas conventionally treated tissue caused endothelial cell death. CONCLUSIONS: This study underlines the detrimental role of glutaraldehyde in the calcification process of bioprosthetic heart valve materials and emphasizes alternative preservation methods that reduce or avoid the use of glutaraldehyde.

Animals↗
PubMed1996

Acceptance of a pump-driven infusion therapy with prostaglandin E1 as a bridge to heart transplantation.

Ambulatory pump-driven intravenous infusions are a novel and - compared with hospitalization-cost-effective procedure to bridge refractory heart failure patients to cardiac transplantation. In the present study 13 patients received chronic infusions with prostaglandin E1 alone or in conjunction with catecholamines and the acceptance of this bridging therapy was investigated over a period of seven weeks. Prostaglandin E1 was uptitrated from 2.5 ng/kg/min to a maximum of 40 ng/kg/min, according to individual tolerance. 50% of the maximum tolerated dose of prostaglandin E1 was used for chronic infusion with a further dose reduction if side effects occurred. Altogether 8 patients who completed the therapy were analysed; of the remaining 5 three patients had a heart transplant, one patient died and one patient did not comply with the protocol. The drugs were administered by an automatic portable pump, which was connected to a subcutaneous tunneled catheter. During hospitalization patients and their relatives were instructed how to prepare drug solutions and to handle the infusion system. Patients' perceptions were investigated by visual analog scale questionnaires (rating scale zero to ten) before, and at weekly intervals during bridging therapy. Initial acceptance was documented as belief in therapy (9.4 +/- 1.2 SD), absence of fear of handling the pump (8.9 +/- 1.2 SD) and confidence of receiving help of close relatives (8.7 +/- 1.8 SD). During the observation period there were no statistically significant differences compared with this favorable starting position and no significant disruption of life style occurred. Pain in the joints-a prostaglandin E1-associated side effect-increased significantly (p < 0.05) at week 5, but returned to baseline levels during the following two weeks. At study end patients confirmed that they would repeat the experience (7.6 +/- 1.4 SD) and advise other patients to undergo this form of therapy (8.2 +/- 1.9 SD). Thus, this pilot study suggests that ambulatory pump-driven intravenous infusion therapy comprising prostaglandin E1 and catecholamines is acceptable to patients as a bridge to heart transplantation and that there should be no major difficulties regarding compliance.

Adult↗
PubMed1995

Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis.

Circulating levels of extracellular matrix components were measured by radioimmunoassays and tested if they were useful for clinical staging in chronic heart failure. In 41 patients with dilated cardiomyopathy (33 idiopathic and 8 ischemic cases), the serum concentrations of procollagen type III aminoterminal peptide (PIIINP), type I collagen telopeptide (ICTP), and basement membrane laminin were significantly higher than in 30 healthy controls regardless of the underlying etiology. Patients with serum values of PIIINP, ICTP, and laminin > 7 micrograms/L, 7.6 micrograms/L, and 2.3 U/ml, respectively, were at higher relative risk for advanced clinical stage, poor hemodynamic condition, hyponatremia, heart transplantation, and death during follow-up than patients with low levels, with the exception that serum laminin > 2.3 U/ml was not significantly associated with hyponatremia and heart transplantation. Despite their interdependence on liver function, circulating levels of PIIINP and ICTP were independent predictors of mortality. In 17 of the 41 patients with cardiomyopathy whose explanted hearts were available for histologic evaluation, serum PIIINP, ICTP, and laminin significantly correlated with the myocardial area fractions of their tissue analogues (PIIINP vs myocardial collagen type III, r = 0.784, p = 0.0013; serum ICTP vs myocardial collagen type I, r = 0.603, p = 0.0527; and serum laminin vs myocardial laminin, r = 0.605, p = 0.0411). In conclusion, the increase in extracellular matrix turnover, which may partially be derived from fibrosis in the myocardium, can be measured in the serum of patients with dilated cardiomyopathy, and has an impact on risk stratification and prognosis.

Cardiomyopathy, Dilated↗
PubMed1995

ICD therapy in survivors of sudden cardiac death awaiting heart transplantation.

The impact of implantable cardioverter defibrillator (ICD) therapy on survival of heart transplant candidates is of major socioeconomic and ethical interest. However, efficacy is even uncertain for patients at highest risk of tachyarrhythmic death on the waiting list. We studied 60 selected heart transplant candidates (mean age, 55.8 years; mean left ventricular ejection fraction, 0.15; functional class III and IV) with a history of successful resuscitation by external electric defibrillation for spontaneous, syncopal ventricular tachyarrhythmia during the study period from March 1992 through September 1994. At the time of registration for transplantation, 30 patients had ICD devices implanted, whereas 30 patients lacked ICD therapy for various nonmedical reasons. Both therapy groups were comparable in clinical and hemodynamic characteristics as well as in intention to transplant (median waiting time to transplantation, 5.7 and 6 months, respectively; not significant by log-rank method). Survival on the waiting list was significantly improved by ICD therapy; only 1 of the 30 ICD patients (19 transplanted) but 7 of the 30 non-ICD patients (14 transplanted) died on the waiting list (p < 0.05 by log-rank method). Implantable cardioverter defibrillator therapy did not affect survival after transplantation as compared with non-ICD patients (not significant by log-rank method). During the waiting time, 26 of the ICD patients (87%) experienced adequate ICD discharges, and 12 of the non-ICD patients were treated successfully by external electric defibrillation (40%).(ABSTRACT TRUNCATED AT 250 WORDS)

Death, Sudden, Cardiac↗
PubMed1995

The impact of implantable cardioverter-defibrillators on mortality among patients on the waiting list for heart transplantation.

Implantable cardioverter-defibrillators were investigated for their impact on mortality in 228 consecutive heart transplant candidates on the waiting list for transplantation (207 patients without and 21 with implantable cardioverter-defibrillator therapy). The mortality rate in 207 patients without implantable cardioverter-defibrillator therapy was 23.2% and in 21 patients with implantable cardioverter-defibrillator therapy was 4.7%. In a Cox proportional hazards model for all 228 study patients (mortality while on the waiting list: 21.5%; transplantation rate: 54.8%), the absence of an implantable cardioverter-defibrillator was only a marginally significant predictor of mortality (p = 0.079). However, the absence of an implantable cardioverter-defibrillator was a powerful predictor of mortality for a subgroup of 134 patients with high-grade ventricular arrhythmias on Holter electrocardiography (mortality while on the waiting list: 26.1%; transplantation rate: 54.5%; p = 0.022) and for a subgroup of 58 survivors of sudden cardiac death (mortality while on the waiting list: 22.4%; transplantation rate: 56.9%; p = 0.018). Implantable cardioverter-defibrillator therapy can be strongly recommended in transplant candidates with a history of sudden cardiac death. Recommendations for an expanded, prophylactic use of implantable cardioverter-defibrillator therapy in heart transplant candidates cannot be given.

Arrhythmias, Cardiac↗
PubMed1995

Tissue polypeptide specific antigen for the detection of lymphoproliferative diseases induced by cyclosporin.

AIM: To evaluate the efficacy of tissue polypeptide specific (TPS) antigen for the early detection of cyclosporin A (CyA) induced post-transplant lymphoproliferative diseases. METHODS: Serum concentrations of TPS antigen were analysed using a monoclonal enzyme immunoassay and whole blood CyA concentrations were measured using high pressure liquid chromatography. Infection with Epstein-Barr virus and cytomegalovirus was detected by determining levels of IgM and IgG antibodies directed against viral capsid antigen (VCA). Immunohistochemistry and analysis of clonality were carried out on formalin fixed, paraffin wax embedded tissue. RESULTS: The mean serum concentration of TPS antigen in the eight transplant recipients investigated was 60 U/l during periods without complication (control), 101 U/l during infection, 166 U/l when the diagnosis of a lymphoma was confirmed, and 172 U/l when lymphoma and infection coincided. Increased TPS antigen concentrations were detected in six patients one month before detection of malignancy. After reduction of immunosuppression and the start of tumour regression, TPS antigen concentrations decreased. TPS antigen concentrations increased in the one patient who experienced a recurrence. CONCLUSIONS: Continuous monitoring of TPS antigen concentrations leads to the early discovery of CyA induced lymphoproliferative disease.

Adult↗
PubMed1995

[Strategies in management of heart transplantation candidates with tachycardic ventricular arrhythmia anamnesis].

We followed up 73 consecutive patients with a history of syncopal ventricular tachyarrhythmias on the waiting list for a heart transplant between 1st March 1992 and 15th September 1994 with the aim of evaluating the impact of implantable cardioverter defibrillator (ICD) on survival. On registration 60 patients were considered fit enough to be ambulant whilst awaiting transplantation. 30 were given ICD therapy (group 1) and 30 were not (group 2). 13 patients required inpatient supervision for ventricular arrhythmias whilst awaiting transplantation, but received no ICD therapy (group 3). The 13 in-patients were in a worse clinical state (NYHA) than the 30 out-patients not given ICD (p < 0.05). With respect to all other clinical and hemodynamic characteristics all groups were comparable. Waiting time for transplantation was also comparable in all groups (n.s., log-rank method). ICD therapy resulted in a significant improvement of survival in these high-risk patients prior to transplantation. Only 1 out of the 30 ICD patients (group 2) and 5 out of the 13 in-patients (group 3) (p < 0.05 log-rank method). During the waiting time group 3 patients were hospitalised longest (p < 0.05), but there was a clear trend that also ICD patients had to be hospitalised to an increased extent (n.s.). Cox multivariate regression analysis of this study population showed that the cardiac index (p = 0.001) and lack of ICD therapy (p = 0.035) were the only independent significant predictors of mortality on the waiting list. ICD therapy had no influence on mortality after transplantation (n.s. log-rank method).

Adult↗
PubMed1995

[Surgery of thoracic and thoraco-abdominal aneurysms using deep hypothermia and cardiovascular arrest with continuous administration of blood cardioplegia].

Between January 1991 and February 1993, 14 patients (3 female, 11 male) aged between 21 and 79 years (mean 50 years) underwent reconstruction of the thoracic (n = 7) and thoracoabdominal aorta (n = 7). Four patients had previously undergone operation of the ascending aorta, in 3 patients coronary artery by pass grafting was performed before. All patients were operated using cardiopulmonary bypass with continuous blood cardioplegia, hypothermic circulatory arrest (11 degrees C nasopharyngeal temperature, 0-EEG) and posterolateral exposure. All patent lower intercostal and lumbar arteries (Th3-L5) were reimplanted. The 30-day mortality after repair of the thoracic aorta was 0, after replacement of the thoracoabdominal aorta 28.5% (n = 2). One patient died 70 days after replacement of the thoracic aorta as a consequence of a perioperative stroke. None of the surviving 11 patients developed a permanent neurologic deficit, renal or cardiac dysfunction. The average intensive care stay was 6 days for patients after replacement of the thoracic and 18 days for patients after replacement of the thoracoabdominal aorta. Our results indicate the method of elective hypothermia and circulatory arrest effective in spinal cord protection. The increase in the tolerable duration of spinal cord ischemia supports the reimplantation of all intercostal and lumbar vessels.

Adult↗
PubMed1995

The use of recombinant human erythropoietin in lung transplantation.

Recombinant human erythropoietin (r-HuEPO) was administered in 4 lung transplant recipients to treat chronic anemia beyond the immediate postoperative period. There were 2 males and 2 females with a mean age of 38 years (range 22-49). None of the patients had major infection or rejection problems, and no blood products were used. Because of different individual responses duration of therapy was 1 to 17 weeks (median 5) with a total dosage ranging from 8 to 36 x 10(3) IU (mean 21 x 10(3)). The median single dose was 58 IU/kg (range 36-100). Hemoglobin levels increased significantly from 9.1 +/- 0.2 to 12.7 +/- 0.3 g/dl (mean +/- SE; p < 0.01). There were no side effects. r-HuEPO is recommended in treatment of chronic anemia in lung transplant patients to save blood products and to exclude the potential risk of transfusion-transmitted viral infections.

Adult↗