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Biomedical subjects

Y Weng

Publications and source records attributed to Y Weng.

At least 55 records · Page 3Linked to original sources

[Pathologic changes of lymphatic capillaries after injection of U14 cells in rat tongue perineoplastic area].

OBJECTIVE: 1. To establish a model of neck lymphatic metastasis of cancer by injecting tumor cells into the rat tongue; 2. To observe the relationship between pathologic changes of perineoplastic lymphatic in different stages of implanted tumor growth and lymphatic metastasis of tumor cells. METHODS: 60 Kunming rats with injection of 5 x 10(6) U14 tumor cells into each rat tongue were chosen and randomized into 6 groups. In every 5 days, specimens of rat tongues with implanted tumor and neck lymph nodes with possible metastatic tumor cells were removed from each group of rats. Cryosections of rat tongue were processed with a modified enzyme-histochemical staining technique, using 5'-nucleotidase with HE to demonstrate lymphatic capillaries. Attention was paid to pathologic change of lymphatic capillaries in perineoplastic area of rat tongue in different growth stages of implanted tumor. Routing wax sections of lymph nodes processed with HE staining were examined under light microscopy to determine whether there were any metastasis tumor cells. RESULTS: 1. Metastasis to neck lymph nodes could be observed 15 days later after injection of U14 tumor cells into rat tongue. The situation of metastasis of lymph nodes varied greatly from tumor cells in bundle within marginal sinus to complete occupation of lymph nodes by U14 cells. 2. Tumor cells penetrated the lymphatic capillary by passing singly or in clumps between endothelial cells or through some destroyed endothelia. A great number of lymphatic with dilated cavity was found nearby the tumor tissue which facilitated tumor cells to enter the lymphatic cavity. 3. There were much more amount of lymphatic capillaries with dilated cavity around tumor mass comparing with that of normal tongue of the control group rats, and the number of lymphatic capillaries with opening cavity tend to increase with growth of implanted tumor. CONCLUSION: Direct and objective view of lymphatic capillaries can be obtained by means of the modified enzyme-histochemical staining technique, using 5'-nucleotidase with HE to demonstrate lymphatic capillaries; A great number of lymphatic capillaries with dented cavity in normal physical state are forced to be dilated during process of tumor growth, thus in turn increase the possibility for tumor cells to penetrate the lymphatic capillary by passing singly or in clumps between endothelial cells.

Animals↗

Medium-term results of heart transplantation using donors over 63 years of age.

BACKGROUND: The continual shortage of hearts for transplantation (HTx) led to the expansion of the donor pool by accepting older donors. We compared the medium-term follow-up of patients after HTx with older hearts (over the age of 63 years) with those of patients after HTx with younger hearts. PATIENTS AND METHODS: Since April 1994 we have used hearts for HTx from donors older than the age of 63 years. Until November 1998, 309 HTx and 9 re-HTx were performed in 309 adults with a mean age of 50.7+/-10.9 years (range 17-68 years). There were 252 men and 57 women. The patients were divided into two groups: group I--donor age under 63 years (296 patients, mean age 50.4+/-11 years; mean donor age 38.1+/-13 years; mean follow-up 1.7+/-1.6 years); group II-donor age of more than 63 years (13 patients, mean age 57.4+/-5.6 years; mean donor age 65.1+/-2.1; mean follow-up 2.2+/-1.6 years). There were no differences in the etiology of heart failure, gender, or ischemia time between the groups. The patients in group II were significantly older (P = 0.008). Multiple factors were analyzed in the groups, which included changes in the left/right ventricle ejection fraction, early postoperative mortality (up to 30 days), cumulative survival rates and cardiac-dependent morbidity [myocardial infarction, malignant arrhythmias, coronary stenosis (>50% in one of the main coronary arteries) and transplant vasculopathy]. Additionally, freedom from cytomegalovirus infection (rise of titer or seroconversion) and freedom of acute rejection episodes grade > or =2 (International Society of Heart & Lung Transplantation [ISHLT]) were analyzed. RESULTS: After 1 year mean left and right ventricle ejection fraction were good in both groups and did not significantly change for up to 2 years. No Re-HTx was performed in group II. The early postoperative mortality was similar in both groups (P = 0.8). Also, the cumulative survival rates were similar in both groups (P = 0.87). Long-term cardiac morbidity was lower in group I (P = 0.03). The long-term freedom from cytomegalovirus infection in group I was significantly higher when compared with group II (P = 0.0002). The long-term freedom from severe rejection episodes was similar in both groups (P = 0.3) CONCLUSION: The study found a significant increase in long-term cardiac morbidity due to more focal coronary stenosis in group II, and freedom from cytomegalovirus infection, but did not find significant differences in the long-term survival between patients who received hearts from donors of up to 63 years of age and from those more than 63 years. The acceptance of donors older than 63 years old for HTx does not worsen the outcome of the recipients. The careful selection of older donors, with close monitoring of the coronary situation after HTx and expanded indications for revascularization of older hearts, could make HTx with older hearts, even in older recipients, a safe option.

Adolescent↗

A critical site in the core of the CCR5 chemokine receptor required for binding and infectivity of human immunodeficiency virus type 1.

Like the CCR5 chemokine receptors of humans and rhesus macaques, the very homologous (approximately 98-99% identical) CCR5 of African green monkeys (AGMs) avidly binds beta-chemokines and functions as a coreceptor for simian immunodeficiency viruses. However, AGM CCR5 is a weak coreceptor for tested macrophage-tropic (R5) isolates of human immunodeficiency virus type 1 (HIV-1). Correspondingly, gp120 envelope glycoproteins derived from R5 isolates of HIV-1 bind poorly to AGM CCR5. We focused on a unique extracellular amino acid substitution at the juncture of transmembrane helix 4 (TM4) and extracellular loop 2 (ECL2) (Arg for Gly at amino acid 163 (G163R)) as the likely source of the weak R5 gp120 binding and HIV-1 coreceptor properties of AGM CCR5. Accordingly, a G163R mutant of human CCR5 was severely attenuated in its ability to bind R5 gp120s and to mediate infection by R5 HIV-1 isolates. Conversely, the R163G mutant of AGM CCR5 was substantially strengthened as a coreceptor for HIV-1 and had improved R5 gp120 binding affinity relative to the wild-type AGM CCR5. These substitutions at amino acid position 163 had no effect on chemokine binding or signal transduction, suggesting the absence of structural alterations. The 2D7 monoclonal antibody has been reported to bind to ECL2 and to block HIV-1 binding and infection. Whereas 2D7 antibody binding to CCR5 was unaffected by the G163R mutation, it was prevented by a conservative ECL2 substitution (K171R), shared between rhesus and AGM CCR5s. Thus, it appears that the 2D7 antibody binds to an epitope that includes Lys-171 and may block HIV-1 infection mediated by CCR5 by occluding an HIV-1-binding site in the vicinity of Gly-163. In summary, our results identify a site for gp120 interaction that is critical for R5 isolates of HIV-1 in the central core of human CCR5, and we propose that this site collaborates with a previously identified region in the CCR5 amino terminus to enable gp120 binding and HIV-1 infections.

Amino Acid Sequence↗

Incidence of atrial flutter/fibrillation in adults with atrial septal defect before and after surgery.

BACKGROUND: There is controversy about the benefit of surgical repair for atrial septal defect in adults, especially its effect on the incidence of supraventricular dysrhythmias, atrial flutter and fibrillation. We studied their incidence before and after operation. METHODS: We examined surface and 24-hour Holter electrocardiograms before, early (between 3 and 7 days), and late (more than 6 months) after operation, performed at age 42.2 years (range, 18.5 to 74.9 years), in 211 adults with atrial septal defect. Patients were arbitrarily divided into three groups: age 18 to 40 years (n = 101), age 40 to 60 years (n = 83), and age more than 60 years (n = 27). All consecutive patients operated on between January 1988 and December 1996 and having a pulmonary to systemic flow ratio of 1.5:1 or greater were included in this study. RESULTS: The age of patients without arrhythmias before or after atrial septal defect closure (39+/-13 years) was significantly lower than that of patients with flutter (54+/-12 years) or fibrillation (59+/-8 years). The incidence of atrial flutter was influenced by surgical repair as atrial flutter converted to sinus rhythm late after operation in 10 of 18 patients. However, there was no change in the incidence of atrial fibrillation before (n = 28) and after (n = 21) operation. CONCLUSIONS: Our data show that surgical correction of atrial septal defect leads to regression of the incidence of atrial flutter but not fibrillation. Thus, surgical repair of atrial septal defect to abolish supraventricular tachyarrhythmias in adults is warranted, but in patients with fibrillation, it may have to be combined with a Maze operation in the future.

Adolescent↗

Cardiac recovery in dilated cardiomyopathy by unloading with a left ventricular assist device.

BACKGROUND: Lasting recovery from intractable end-stage dilated cardiomyopathy, which occurs with ventricular unloading, has recently been demonstrated in 5 patients. Here our extended clinical experience with the "weaning" concept is presented. METHODS: In 19 patients (23 to 65 years) with intractable end-stage dilated cardiomyopathy, ventricular assist devices were explanted after support periods of up to 26 months, when repeat off-pump studies had shown either restoration of cardiac function (left ventricular ejection fraction, > 45%) and dimensions (left ventricular internal diameter in diastole, < 55 mm) or partial recovery (left ventricular ejection fraction between 35% and 40%) with serious complications on the device. At the time of device placement left ventricular ejection fraction was below 20% and left ventricular internal diameter in diastole more than 64 mm and bridge-to-transplantation had been planned. RESULTS: Seven patients with persistently restored cardiac function for more than 8 months and 5 patients for less than 5 months after weaning were studied. Five patients with recurrent heart failure died within 4 to 8 months after explantation. Four patients had to be transplanted and 2 died for reasons unrelated to cardiac function. An individual optimal left ventricular ejection fraction and left ventricular internal diameter in diastole was reached before pump removal was actually conducted in all patients. These parameters gradually deteriorated until pump removal. CONCLUSIONS: Lasting recovery can be reached by ventricular unloading in a subset of patients with intractable end-stage dilated cardiomyopathy. Obviously, there is an individual optimum of recovery that cannot be further improved by prolonged unloading.

Adult↗

The Cox maze iii procedure: parallel normalization of sinus node dysfunction, improvement of atrial function, and recovery of the cardiac autonomic nervous system.

OBJECTIVE: The Cox maze III procedure includes isolation of the pulmonary veins and multiple incisions in both atria in what corresponds to partial autotransplantation and partial denervation of the heart. The aim of this prospective longitudinal study was to identify physiologic effects of reinnervation on changes in heart rate at rest and in response to various stimulations and on atrial function after the Cox maze III procedure. PATIENTS AND METHODS: Power spectral analysis of heart rate variability, exercise testing, 24-hour Holter monitoring, electrocardiography, and transthoracic and transesophageal echocardiography were performed in 30 adult patients after the combined Cox maze III procedure and mitral valve surgery (maze group). They were prospectively followed up at 1, 3, 6, and 12 months after the operation. The results were compared with those of 15 heart transplant recipients (transplant group) and normal probands (healthy adults, n = 12). RESULTS: The physiologic effects of denervation with no differences in cardiac autonomic activity between the groups were seen early after the operation. Later, evidence of autonomic reinnervation was observed only in the maze group but not in the transplant group. Inappropriate heart rate responses during physical exercise were clearly evident in both groups after 1 and 3 months, with progressive improvement seen between 6 and 12 months only in the maze group. Left atrial function after the Cox maze procedure improved parallel to the recovery of sinus node function. CONCLUSION: Progressive improvement of sinus node function and atrial contractions with significant functional normalization 1 year after the Cox maze procedure corresponded to functional reinnervation and recovery of the autonomic nervous system.

Adult↗

Coronary artery bypass grafting after orthotopic heart transplantation.

OBJECTIVE: Graft coronary disease (GCD) remains the major determinant of long-term survival after heart transplantation. Therapeutic strategies for the prevention or retardation of GCD in the cardiac allograft are limited, and palliative surgical coronary revascularization has been attempted. The aim of this report was to retrospectively analyze our results of coronary artery bypass grafting after cardiac transplantation. This paper correlates the outcome of patients with the pathohistological and angiographic type of lesion in order to identify transplant recipients who may profit from surgical myocardial revascularization. METHODS: Seven patients with a mean age of 55 years (range 45-61 years) underwent coronary artery bypass grafting as a result of GCD at a mean of 67 months (range 6-128 months) after cardiac transplantation. By the inclusion of the clinical history and the angiographic pattern of GCD lesions, the primary indications for surgical revascularization, operative results, pathohistological studies and follow-ups were examined. RESULTS: Elective surgery was performed in two patients with proximal, severe triple vessel disease (Type A lesion) and in one patient in whom the primary reason for cardiac surgery was severe tricuspid regurgitation. This patient electively received a tricuspid valve replacement and concomitant single vessel bypass surgery for proximal GCD (Type A lesion). Emergency surgery was performed in four patients: preoperatively three patients post-infarction developed worsening congestive heart failure, which resulted in low cardiac output syndrome. One patient with combined Types A and B/C lesions required emergency surgery for dissection of the right coronary artery (RCA) after an angioplasty procedure. Angiographically all these patients showed diffuse, distal arteriopathy (combined Type B/C lesions). The electively operated patients (n = 3) and the patient with dissection of the RCA (n = 1) had successful operations and survived beyond hospital discharge (overall survival for coronary artery bypass graft (CABG) in GCD patients 4 out of 7; 57%). All three patients with distal arteriopathy, who underwent emergency surgery, died in hospital from left ventricular failure (43%). The four patients discharged from hospital with a mean follow-up of 10 months (range 2-32 months) are all in good clinical condition. CONCLUSIONS: Coronary artery bypass grafting can be successfully performed in a subgroup of cardiac transplant patients with Type A lesions. However, the state of diffusely diseased distal arteries (Type B/C lesions), which is prevalent in this group of patients, limits the use of bypass surgery.

Biopsy↗

Comparison of acute effects on right ventricular haemodynamics of surgical versus interventional closure of atrial septal defects.

OBJECTIVES: We compared the acute effects on right ventricular haemodynamics of surgical versus transcatheter closure of medium-sized atrial septal defects. METHODS: We studied 47 consecutive patients with a defect in the oval fossa and a ratio of pulmonary to systemic flows between 1.5: 1 and 2: 1. They were divided into two groups according to whether the defects were closed by surgery, performed in 23 patients, or by interventional catheterization, achieved in 24 patients. By means of transthoracic cross-sectional echocardiography, we measured right ventricular end-diastolic and endsystolic volumes and calculated ejection fractions. These calculations were performed before, and between 1 and 7 days after closure of the defect. RESULTS: Before closure of the defect, all patients had an enlarged right ventricle with normal function. After closure by either method, there was no difference in the rate of normalization of end-diastolic volume, but endsystolic volume remained enlarged. Thus, the calculated ejection fraction was lower than before closure. CONCLUSIONS: There was no difference in right ventricular volumes or function early after closure of atrial septal defects, irrespective of whether this was achieved surgically or via transcatheter closure.

Adolescent↗

Radiologic anatomy of ventricular assist devices.

Ventricular assist devices (VAD) allow for long-term circulatory support of patients with end-stage heart failure. With the increasing duration of circulatory support, diagnostic imaging plays an important role in the management of patients on a VAD. The aim of our review was to analyze the radiologic features of different VADs. From 1987 to 1996, 319 patients (mean age 42 years, range 3 to 74 years) were treated with a VAD. A Berlin Heart VAD was implanted in 263 of the patients, the univentricular Baxtor Novacor was implanted in three patients, and the univentricular CI Heartmate was implanted in 19 patients. All patients were studied by serial chest radiographs. In addition, 70 patients underwent computed tomography (CT), and five patients underwent electron beam CT. The Berlin Heart VAD was used as a biventricular support system in 218 patients. In all cases, the position of the wire-directed cannulae was identified on the chest radiographs, while the exact position of the cannula tip could be visualized by CT only. The plastic cannulae of both the Novacor and the Heartmate were not discernible on radiographs, but required CT for evaluation. Computed tomography also resolved the metal components of the pumps. The titanium-made pump housing of the Heartmate caused beam-hardening artefacts that might conceal fluid accumulations in the pump pocket. Computed tomography is the standard of reference for examinations of cannula position, pump position, and pump components of ventricular assist devices.

Adolescent↗

A quantitative MR study of the hippocampal formation, the amygdala, and the temporal horn of the lateral ventricle in healthy subjects 40 to 90 years of age.

BACKGROUND AND PURPOSE: Several investigators have defined normal age-specific values for the medial temporal lobe structures in neurologically normal elderly subjects, but, to our knowledge, no one has reported those values for a large sample of healthy volunteers. The purpose of our study was to define normal age-specific values for the hippocampal formation, the amygdala, and the temporal horn of the lateral ventricle by age group, ranging from 40 to 90 years, in order to generate a guideline for the quantitative MR diagnosis and differential diagnosis for early Alzheimer disease. METHODS: MR-based volumetric measurements of the hippocampal formation, the amygdala, and the temporal horn, standardized by total intracranial volume, were obtained from oblique coronal and sagittal T1-weighted MR images in 619 healthy volunteers and two cadaveric specimens. RESULTS: Differences in standardized volumes of the hippocampal formation, the amygdala, and the temporal horn were significant among the 61- to 70-year-old, 71- to 80-year-old, and 81- to 90-year-old groups, and were not significant between the 40- to 50-year-old and 51- to 60-year-old groups. We found no significant differences in side or sex among the age groups for any of the structures. CONCLUSION: Differences in the mean value and in the 95% normal range of standardized volumes of the hippocampal formation, the amygdala, and the temporal horn correspond to differences in age among healthy subjects; therefore, age should be considered a factor in correlative research, especially in that involving patients in the early stages of Alzheimer disease.

Adult↗

Partial functional deficiency of E160D flap endonuclease-1 mutant in vitro and in vivo is due to defective cleavage of DNA substrates.

To assess the roles of the active site residues Glu160 and Asp181 of human FEN-1 nuclease in binding and catalysis of the flap DNA substrate and in vivo biological processes of DNA damage and repair, five different amino acids were replaced at each site through site-directed mutagenesis of the FEN-1 gene. The mutants were then expressed in Escherichia coli and purified using a His-tag. Even though the mutants bind to the flap DNA to different degrees, most of the mutants lost flap nuclease activity with the exception of an E160D mutant. This mutant retained wild type-like binding ability, specificity, and partial catalytic activity. Detailed steady state and pre-steady state kinetic analysis revealed that the functional deficiency of this mutant was due to retardation of the endonucleolytic cleavage. When the mutant enzyme E160D was expressed in yeast, it partially complements the biological functions of the homologous yeast gene, RAD27, and reverses the hyper-temperature lethality and hypersensitivity to methyl methanesulfonate, in a manner corresponding to the in vitro activity.

Base Sequence↗

Newly discovered archaebacterial flap endonucleases show a structure-specific mechanism for DNA substrate binding and catalysis resembling human flap endonuclease-1.

Mammalian flap endonuclease-1 (FEN-1) is a structure-specific metalloenzyme that acts in processing of both the Okazaki fragments during lagging strand DNA synthesis and flap intermediates during DNA damage repair. We identified and cloned three open reading frames encoding a flap endonuclease from Archaeglobus fulgidus, Methanococcus jannaschii, and Pyrococcus furiosus, respectively. The deduced FEN-1 protein sequences share approximately 75% similarity with the human FEN-1 nuclease in the conserved nuclease domains, and extensive biochemical experiments indicate that the substrate specificities and catalytic activities of these enzymes have overall similarities with those of the human enzyme. Thus, FEN-1 enzymes and likely reaction mechanisms are conserved across the eukaryotic and archaeal kingdoms. Detailed comparative analysis, however, reveals subtle differences among these four enzymes including distinctive substrate specificity, tolerance of the archaebacterial enzymes for acidic pHs and elevated temperatures, and variations in the metal-ion dependence of substrate cleavage. Although the archaebacterial enzymes were inactive at temperatures below 30 degreesC, DNA binding occurred at temperatures as low as 4 degreesC and with or without metal ions. Thus, these archaeal enzymes may provide a means to dissect the specific binding and catalytic mechanisms of the entire FEN-1 family of structure-specific nucleases.

Acids↗

Binding and functional properties of recombinant and endogenous CXCR3 chemokine receptors.

IP10 and MIG are two members of the CXC branch of the chemokine superfamily whose expression is dramatically up-regulated by interferon (IFN)-gamma. The proteins act largely on natural killer (NK)-cells and activated T-cells and have been implicated in mediating some of the effects of IFN-gamma and lipopolysaccharides (LPSs), as well as T-cell-dependent anti-tumor responses. Recently both chemokines have been shown to be functional agonists of the same G-protein-coupled receptor, CXCR3. We now report the pharmacological characterization of CXCR3 and find that, when heterologously expressed, CXCR3 binds IP10 and MIG with Ki values of 0.14 and 4.9 nM, respectively. The receptor has very modest affinity for SDF-1alpha and little or no affinity for other CXC-chemokines. The properties of the endogenous receptor expressed on activated T-cells are similar. Surprisingly, several CC-chemokines, particularly eotaxin and MCP-4, also compete with moderate affinity for the binding of IP10 to CXCR3. Eotaxin does not activate CXCR3 but, in CXCR3-transfected cells, can block IP10-mediated receptor activation. Eotaxin, therefore, may be a natural CXCR3 antagonist.

Animals↗

The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs.

The nonsense-mediated mRNA decay pathway is an example of an evolutionarily conserved surveillance pathway that rids the cell of transcripts that contain nonsense mutations. The product of the UPF1 gene is a necessary component of the putative surveillance complex that recognizes and degrades aberrant mRNAs. Recent results indicate that the Upf1p also enhances translation termination at a nonsense codon. The results presented here demonstrate that the yeast and human forms of the Upf1p interact with both eukaryotic translation termination factors eRF1 and eRF3. Consistent with Upf1p interacting with the eRFs, the Upf1p is found in the prion-like aggregates that contain eRF1 and eRF3 observed in yeast [PSI+] strains. These results suggest that interaction of the Upf1p with the peptidyl release factors may be a key event in the assembly of the putative surveillance complex that enhances translation termination, monitors whether termination has occurred prematurely, and promotes degradation of aberrant transcripts.

Fungal Proteins↗

Daily noninvasive rejection monitoring improves long-term survival in pediatric heart transplantation.

BACKGROUND: Acute rejection episodes and transplant vasculopathy (TVP) account for most of the late deaths after heart transplantation in both adults and children. Accumulating evidence indicates that fatal acute rejection and TVP are related to unrecognized and untreated early and ongoing acute rejection. Day-by-day surveillance of the heart and prompt treatment of any rejection may yield improved long-term survival. METHODS: In almost all patients having transplantation at our institution (978 patients since 1986), the intramyocardial electrogram (IMEG) was recorded routinely every day through a telemetry pacemaker and transmitted to our center by telephone modem. Earlier studies showed a substantial voltage drop in the IMEG QRS complex is highly indicative of acute rejection, including humoral rejection. In this study, we reviewed the data from 69 pediatric patients up to 16 years old for the incidence of acute rejection, TVP, and long-term outcome. Diagnostic endomyocardial biopsies were performed in only 10 patients, and recent coronary angiograms from 29 children were reviewed. RESULTS: In 50 children discharged after heart transplantation, IMEG surveillance data for a mean of 2.9 years indicated 72 acute rejection episodes. During follow-up of 1 month to 10.5 years (mean follow-up, 4.4 years), 2 patients died late of causes unrelated to either rejection or TVP. Another patient died of rejection during unrecognized underimmunosuppression nearly 8 years after transplantation and nearly 31/2 years after discontinuing IMEG recordings. Two patients without IMEG recording died of acute rejection or late TVP. In 1 patient, moderate TVP was seen on an angiogram after 41/2 years (incidence, 2.0%; 5-year incidence, 5.6%). CONCLUSIONS: Daily recording of the IMEG can reliably detect early stages of acute rejection episodes, and immediate rejection treatment seems to keep the incidence of TVP low. The IMEG appears better than all the other rejection monitoring protocols currently in use.

Acute Disease↗

Circulatory support with pneumatic paracorporeal ventricular assist device in infants and children.

BACKGROUND: Mechanical circulatory support in intractable heart failure in children has been limited to centrifugal pumps and extracorporeal membrane oxygenation: Since 1990 small adult-size pulsatile air-driven ventricular assist devices "Berlin Heart" (VAD) and, since 1992 miniaturized pediatric VAD (12, 15, 25, 30 mL pumps), have been used in our institution. Since 1994 the blood-contacting surfaces of the device system have been heparin-coated. In this report the experiences with VAD support in 28 children are presented. METHODS: In 28 children-ages between 6 days and 16 years-the Berlin Heart VAD has been applied for periods of between 12 hours and 98 days (mean, 16.9 days) aiming at keeping the patient alive and allowing for recovery from shock sequelae until later transplantation or myocardial recovery. There were three groups. Group I: with primary intention of "bridge-to-transplantation" in various forms of cardiomyopathy (n = 13) or chronic stages of congenital heart disease (n = 5). Group II: "Rescue" in intractable heart failure early after corrective surgery for congenital heart disease (n = 4) or in early graft failure after a heart transplantation (n = 1). Group III: "Acute myocarditis" (n = 5) aiming at either myocardial recovery or transplantation. Twelve were brought to the operating room under cardiac massage and 25 had been on the respirator for more than 24 hours. RESULTS: Twelve patients died on the system from sequelae of profound shock-multiorgan failure, sepsis, loss of peripheral circulatory resistance-or from hemorrhagic complications (n = 4) or brain death (n = 1). Thirteen patients (groups I and III) were transplanted after support periods of between 3 and 98 days with 7 long-term survivors living now up to 7.5 years (mean, 4.4 years). Three patients (groups II and III) were weaned from the system with two long-term survivors (both in group III). There were no patients in group II who survived and the "rescue" indication has been discarded for VAD since 1992. Such patients are since treated by extracorporeal membrane oxygenation (ECMO) in our institution. Out of the 8 patients placed on VAD during 1996 and 1997, 7 were successfully supported until transplantation or weaning. Thirteen patients were extubated and mobilized on the system. Whereas with the earlier systems thrombi in the blood pumps were seen in 15 instances and 2 patients suffered from thromboembolic complications, no thrombotic events occurred with the heparin-coated systems. CONCLUSIONS: After accumulating clinical experience and several technical improvements since 1990 the use of the pediatric Berlin Heart VAD has matured into a reliable and safe system to keep patients with otherwise intractable heart failure alive until complete myocardial recovery is reached or transplantation becomes feasible. Whereas heart failure early after cardiac operation is now primarily treated by ECMO, acute myocarditis appears to be a promising precondition for complete cardiac recovery during VAD support.

Adolescent↗