Effect of obesity on outcome after cardiac transplantation.
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Adult↗
Biomedical subjects
G Laufer
Publications and source records attributed to G Laufer.
Impact of gender mismatch on the outcome of heart transplantation.
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Adult↗
Noninvasive monitoring of peak filling rate with acoustic quantification echocardiography accurately detects acute cardiac allograft rejection.
BACKGROUND: Acute cardiac allograft rejection is associated with early diastolic dysfunction. The development of chronic rejection is dependent on the frequency and severity of acute rejection episodes. Therefore, early diagnosis and therapy influence long-term survival significantly. For the first time, acoustic quantification, a new echocardiographic technology for on-line measurement of cardiac volumes and their changes, facilitates quantitative assessment of systolic and diastolic function noninvasively. METHODS: Since May 1996, all consecutive patients after cardiac transplantation (n = 94) underwent 475 endomyocardial biopsies and the same number of echocardiographic studies within 6 hours after biopsy before the histological results were available. RESULTS: Nineteen patients showed 23 episodes of acute rejection (ISHLT > or = 2). There was a significant decrease in left ventricular peak filling rate [PFR: end-diastolic volume (EDV)/ second) as a parameter of diastolic function during rejection (2.9 +/- 0.4, n = 23) as compared to PFR measured under nonrejection status (4.5 +/- 0.8; n = 452; p < 0.0001). Most importantly we found that in these 19 patients showing rejection, the PFR was normal in the last examination before rejection, but was significantly reduced during rejection (2.9 +/- 0.4 vs 4.5 +/- 0.7; n = 23, p < 0.0001). After successful rejection therapy, PFR again normalized in all patients, with the exception of 1 patient with steroid-refractory humoral rejection. We calculated sensitivity and specificity for several cutpoints for the event "first rejection" in 15 patients and plotted them in a receiver operating characteristic curve, showing that a PFR > or = 4.0 EDV/second is never associated with treatable rejection. A decrease of PFR of more than 18% from its prevalue of the last biopsy with no rejection increases the accuracy for the diagnosis of rejection significantly. CONCLUSIONS: We conclude that diastolic dysfunction during acute cardiac allograft rejection can be accurately detected by noninvasive measurement of peak filling rate with acoustic quantification echocardiography. Monitoring of this parameter provides reliable discrimination between treatable and nontreatable rejection.
Acute Disease↗
Bridging to heart transplantation: prostaglandin E1 versus prostacyclin versus dobutamine.
BACKGROUND: Prostaglandin E1 (PGE1) and prostacyclin have potent pulmonary and systemic vasodilating properties. This prospective, randomized trial compared PGE1 vs prostacyclin vs. low-dose dobutamine in patients with low-output heart failure awaiting heart transplantation (HTx) who were refractory to oral treatment. METHODS: Patients in advanced heart failure in New York Heart Association (NYHA) Class IV, with a cardiac index < or = 2.5 L/minute/m2 and a pulmonary capillary wedge pressure > or = 20 mmHg, who were listed for HTx were studied. In an inpatient study phase of 12 hours duration, therapy was aimed to increase cardiac output by 20% or more, when compared to baseline values, and to achieve a reduction of pulmonary vascular resistance below 550 dyn.s/cm-5m-2. During a long-term outpatient phase, the drugs were continuously infused to bridge these patients to HTx using three combined negative endpoints (worsening heart failure, serious adverse events, death) for analysis. RESULTS: Sixty-eight patients were enrolled, 30 patients on PGE1, 8 patients on prostacyclin, and 30 patients on dobutamine. During the inpatient study phase, maximum doses were 22 +/- 1.8 ng/kg/minute for PGE1, 7 +/- 1 ng/kg/minute for prostacyclin and 5 +/- 0.4 micrograms/kg/minute for dobutamine. During the inpatient study phase 21 patients failed, 4/30 (13%) patients on PGE1, 4/8 patients on prostacyclin (50%), and 13/30 (43%) on dobutamine (p < 0.05). Long-term continuous intravenous drug infusion in outpatients was begun in 26 patients on PGE1, in 4 patients on prostacyclin, and in 17 patients on dobutamine. Infusion therapy lasted for 88 +/- 14 days in the PGE1 group with 31 +/- 22 days in the prostacyclin group, and 30 +/- 8 days in the dobutamine group (NS). During the outpatient phase 23 patients reached a negative endpoint with 16 patients developing worsening heart failure, 5 severe adverse events and 2 deaths. Seven out of 26 (27%) failed on PGE1, 4/4 (100%) failed on prostacyclin, and 12/17 (71%) failed on dobutamine (p < 0.05, log rank test). Because prostacyclin treatment was ineffective in the first 8 patients, this trial arm was stopped prematurely. CONCLUSIONS: The findings from this prospective open pilot trial suggest that continuous PGE1 infusions at individualized dosages can be useful in certain patients as a pharmacologic bridging procedure with reduced risk to develop worsening heart failure before HTx compared to prostacyclin and dobutamine. Further comparative studies are warranted to investigate the effects of PGE1 among other bridging agents.
Alprostadil↗
Alterations in the number of circulating leucocytes, phenotype of monocyte and cytokine production in patients undergoing cardiothoracic surgery.
Changes in the differential blood cell count, monocyte phenotype and the cytokine plasma levels in a group of seven patients with cardiac surgery/cardiopulmonary bypass (CPB) and nine patients with thoracic surgery/without CPB, both receiving identical opioid-based anaesthetic technique, were assessed. A significant reduction in the number of circulating lymphocytes and monocytes was observed after anaesthesia and surgery. Interestingly, at the end of surgery as well as 1 day post-surgery a marked increase in the number of granulocytes was noted. General anaesthesia and surgery caused a significant reduction of HLA-DR and CD11c/CD18 molecules, starting immediately after induction of anaesthesia, and an increase of CD64 at day 1 after anaesthesia. The use of a CPB was followed by a significant reduction of CD32, CD16, CD54 and HLA-ABC antigens expression at the end of surgery. One day after surgery these parameters returned nearly to baseline values with the exception of CD54. A monocyte subpopulation, characterized by low CD14, high CD16 and HLA-DR expression (CD14+CD16+HLA-DR++) was found in both groups at each time point, and the percentage of this cell subset decreased from baseline to 24 h. The plasma concentrations of IL-6 and IL-10 increased considerably during CPB. No dynamic changes of IL-1 level due to surgery or CPB were found. We conclude that anaesthesia as well as the use of CPB induced profound alterations in the number of circulating leucocytes, and in the phenotype of monocyte and cytokine production.
Aged↗
IgG subclass reactivity to human cardiac myosin in cardiomyopathy patients is indicative of a Th1-like autoimmune disease.
Studies performed in mice together with the demonstration of increased levels of heart-specific autoantibodies, cytokines and cytokine receptors in sera from cardiomyopathy (CMP) patients argued for a pathogenic role of autoimmune mechanisms in CMP. This study was designed to analyse the presence of IgG anti-heart antibodies in sera from patients suffering from hypertrophic and dilatative forms of CMP as well as from patients with ischaemic heart disease and healthy individuals. Patients' sera were analysed for IgG reactivity to Western-blotted extracts prepared from human epithelial and endothelial cells, heart and skeletal muscle specimens as well as from Streptococcus pyogenes. The IgG subclass (IgG1-4) reactivity to purified human cardiac myosin was analysed by ELISA. While sera from CMP patients and healthy individuals displayed comparable IgG reactivity to a variety of human proteins, cardiac myosin represented the prominent antigen detected strongly and preferentially by sera from CMP patients. Pronounced IgG anti-cardiac myosin reactivity was frequently found in sera from patients with dilatative CMP and reduced ventricular function. ELISA analyses revealed a prominent IgG2/IgG3 anti-cardiac myosin reactivity in CMP sera, indicating a preferential Th1-like immune response. Elevated anti-cytomegalovirus, anti-enterovirus IgG titres as well as IgG reactivity to nitrocellulose-blotted S. pyogenes proteins were also frequently observed in the group of CMP patients. If further work can support the hypothesis that autoreactivity to cardiac myosin represents a pathogenic factor in CMP, specific immunomodulation of this Th1- towards a Th2-like immune response may represent a promising therapeutic strategy for CMP.
Adolescent↗
Renal hemodynamic effects of L-arginine and sodium nitroprusside in heart transplant recipients.
BACKGROUND: Long-term treatment with cyclosporine A (CsA) induces vasoconstriction in the kidney and causes renal impairment. An altered L-arginine (L-Arg)/nitric oxide (NO) pathway may play a key role in CsA nephrotoxicity. METHODS: We studied the effect of L-Arg (dosage, 17 mg/kg/min over 30 min), the precursor of NO synthesis, and sodium nitroprusside (SNP; dosage, 1.0 microgram/kg/min over 30 min) on renal hemodynamics in a double-blind, placebo-controlled, randomized, three-way cross-over study comprising 12 stable cardiac transplant recipients on long-term CsA treatment, 10 patients with chronic nephropathy not receiving CsA, and 13 healthy controls. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by paraaminohippurate (PAH) and the inulin clearance method, respectively. RESULTS: In healthy subjects, L-Arg induced an increase in RPF (P = 0.009) and GFR (P = 0.001). By contrast, L-Arg did not induce renal hemodynamic effects in heart transplant patients or patients with chronic nephropathy. SNP reduced RPF (P = 0.050) and GFR (P = 0.005) in patients with chronic nephropathy but did not affect renal hemodynamics in heart transplant recipients or in healthy subjects. CONCLUSIONS: These data indicate that L-Arg cannot be used to reverse CsA-induced renal vasoconstriction in heart transplant recipients under long-term CsA treatment, although these patients have a normal renal response to SNP.
Aged↗
Evaluation of the EMIT Mycophenolic Acid Assay from Dade Behring.
The Emit Mycophenolic Acid Assay, a new homogeneous enzyme immunoassay for the quantitative analysis of mycophenolic acid (MPA) in human plasma, was evaluated and compared to a high-performance liquid chromatography (HPLC) method. Coefficients of variation (CV) of the within-run imprecision (n = 10) varied from 2.5% to 4.4% and from 1.3% to 4.9% for the Emit and the HPLC, respectively. The CV's of between-day imprecision (n = 10) ranged from 7.9% to 10.8% for the Emit and from 4.7% to 12.1% for the HPLC. Mean recoveries were 95.6% and 100.1% for Emit and HPLC, respectively. Serial dilution of a patient pool demonstrated a linear relationship between expected (x) and measured (y) concentrations: Emit, y = 0.998x + 0.086; HPLC, y = 1.006x - 0.016. The detection limit and the lower limit of quantification were 0.087 mg/L and 0.20 mg/L for Emit. The detection limit for HPLC was 0.08 mg/L using a signal-to-noise ratio of three. Sample stability under various storage conditions was satisfactory, although storage at -20 degrees C is recommended for storage longer than one day. No cross-reactivity from the major metabolite mycophenolic acid glucuronide (MPAG) was found. A correlation study on 261 patient samples yielded the following regression equation (bivariate Deming procedure): Emit = 1.012HPLC + 0.244, r = 0.970.
Adult↗
In vitro analysis of alpha-amanitin-resistant transcription from the rRNA, procyclic acidic repetitive protein, and variant surface glycoprotein gene promoters in Trypanosoma brucei.
In Trypanosoma brucei, transcription resistant to the mushroom toxin alpha-amanitin is not restricted to the rRNA genes (rDNA), as in higher eukaryotes, but extends to genes encoding the major cell surface proteins variant surface glycoprotein (VSG) and procyclin or procyclic acidic repetitive protein (PARP). Here, we report the development of a homologous cell extract from procyclic T. brucei cells in which rDNA and PARP A and VSG gene promoters drive efficient, accurate, and alpha-amanitin-resistant transcription. A comparative analysis revealed that transcription from the three promoters generally required identical reaction conditions for maximal efficiency. Nevertheless, PARP promoter transcription proved to be exceptional by its high efficiency, its lag phase, a high template DNA concentration optimum, and its tolerance to increasing concentrations of Mn(2+). Mutational analysis for both the PARP and rDNA promoters showed that the proximal and distal core elements were essential for efficient transcription in vitro. Deletion of the upstream control regions (UCRs), however, had a different effect. Whereas PARP UCR deletion reduced transcription efficiency almost 10-fold, deletion of the rDNA UCR had only a minor effect on transcription efficiency.
Amanitins↗
A simple HPLC method for monitoring mycophenolic acid and its glucuronidated metabolite in transplant recipients.
Mycophenolic acid (MPA) is nowadays in broad clinical use as a substitute for azathioprine. An immunoassay for MPA recently received approval for clinical applications. The high performance liquid chromatography (HPLC) assay for measuring MPA and its glucuronide conjugate (MPAG) we describe here is not only rapid and simple but also extremely sensitive at plasma levels obtained during standard immunosuppressive regimens. The determination of MPAG is possible without any change of the chromatographic conditions (detection wavelength of 214 nm, mobile phase: acetonitrile and 50 mmol/l o-phosphoric acid (50:50, V/V), run time: 15 min). The required equipment is a standard HPLC system including a simple UV-detector. Sample volume of 400 microl is required for both determinations. Detection limit is 0.25 micromol/l for MPA and 5 micromol/l for MPAG. Linearity is excellent for serial dilutions (0.5-25 micromol/l for MPA, 25-500 micromol/l for MPAG) and high accuracies favour the method described. More than 2000 plasma samples tested for MPA in patients after heart transplantation within one year and more than 500 samples for MPAG underline the clinical applicability of this assay.
Blood Chemical Analysis↗
Combined heart and kidney transplantation using a single donor: a single center's experience with nine cases.
BACKGROUND: Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single center's experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. METHODS: From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. RESULTS: One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44+/-28 months. CONCLUSION: HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.
Adult↗
Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT: correlation with histopathology in explanted hearts.
OBJECTIVES: We examined the relationship among viability assessment by dobutamine echocardiography (DE), positron emission tomography (PET) and thallium-201 single-photon emission computed tomography (TI-SPECT) to the degree of fibrosis. BACKGROUND: DE, PET and TI-SPECT have been shown to be sensitive in identifying viability of asynergic myocardium. However, PET and TI-SPECT indicated viability in a significant percentage of segments without dobutamine response or functional improvement after revascularization. METHODS: Twelve patients with coronary artery disease and severely reduced left ventricular function (EF 14.5+/-5.2%) were studied with DE prior to cardiac transplantation: 5 had additional PET and 7 had TI-SPECT studies. Results of the three techniques were compared to histologic findings of the explanted hearts. RESULTS: Segments with >75% viable myocytes by histology were determined to be viable in 78%, 89% and 87% by DE, PET and TI-SPECT; those with 50-75% viable myocytes in 71%, 50% and 87%, respectively. Segments with 25-50% viable myocytes showed response to dobutamine in only 15%, but were viable in 60% by PET and 82% by TI-SPECT. Segments with <25% viable myocytes responded to dobutamine in 19%; however, PET and TI-SPECT demonstrated viability in 33% and 38%, respectively. Discrepant segments without dobutamine response but viability by PET and SPECT had significantly more viable myocytes by pathology than did those classified in agreement to be nonviable but had significantly less viable myocytes than those classified in agreement to be viable (p < .001). CONCLUSIONS: These findings suggest that contractile reserve as evidenced by a positive dobutamine response requires at least 50% viable myocytes in a given segment whereas scintigraphic methods also identify segments with less viable myocytes. Thus, the methods may provide complementary information: Nuclear techniques appear to be highly sensitive for the detection of myocardial viability, and negative tests make it highly unlikely that a significant number of viable myocytes are present in a given segment. Conversely, dobutamine echo may be particularly useful for predicting recovery of systolic function after revascularization.
Aged↗
[Protein catabolism after lung transplantation and heart transplantation].
Any surgical intervention is associated with an activation of protein catabolism, the extent of which is dependent on the severity of surgical trauma. There is a paucity of reports on protein catabolism after transplantation of chest organs (lung transplantation (LTX) and heart transplantation (HTX)). The aim of the present study was to quantify and compare the extent of postoperative protein catabolism and associated metabolic perturbations in patients after LTX and HTX. Eighteen consecutive patients after LTX and 15 consecutive patients after HTX who required postoperative intensive care for more than 4 days, constituted the study population. The nitrogen balance (assessed on the basis of the urea nitrogen production rate and nitrogen intake) was assessed retrospectively and correlated with insulin requirements, immunosuppression and the clinical course. Within the first 5 days the nitrogen balance became progressively negative in both groups, reaching a maximum on the 5th day. Thereafter the nitrogen balance of patients following LTX remained negative, whereas the nitrogen balance of patients following HTX tended to improve. The evolution of nitrogen balance significantly differed between both groups (p < 0.01). The mean nitrogen loss was -0.29 +/- 0.17g/kg BW/day after LTX versus -0.22 +/- 0.12g/kg BW/day after HTX. Smaller amounts of glucocorticoids were used for immunosuppression in patients after HTX than in patients after LTX; nevertheless, heart transplant recipients required higher doses of insulin to maintain normoglycemia. A regression analysis revealed that the duration of stay at the intensive care unit (p < 0.001) and the amount of glucocorticoids (p < 0.01) negatively affected the nitrogen balance, whereas an increased protein intake (p < 0.001) exerted a positive effect. Compared to other major surgical procedures, protein catabolism is excessively elevated in patients after thoracic transplantation. Immunosuppressive therapy with glucocorticoids contributes to protein degradation; the nitrogen balance after LTX is more negative than that after HTX because of higher glucocorticoid requirements following LTX. More aggressive nutritional intervention and especially an increased nitrogen intake might help to reduce protein losses in these patients.
Adult↗
Inhibition of inosine monophosphate dehydrogenase activity by the plasma of heart transplant recipients receiving mycophenolate mofetil.
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Cell Line↗
Pharmacokinetics of mycophenolate mofetil in heart transplant recipients.
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Glucuronates↗
Operations on the thoracic aorta and hypothermic circulatory arrest: is aprotinin safe?
INTRODUCTION: The safety of aprotinin, especially when used with profound hypothermic circulatory arrest, is still a matter of intense debate despite its presumed salutary effects on blood loss. Many investigators have reported toxic renal effects of high-dose aprotinin in such patients, but no prospective, randomized study has been conducted. To assess the potential detrimental effect of aprotinin on renal function and its putative reduction of blood loss, 50 patients undergoing thoracic aortic operations with the use of profound hypothermic circulatory arrest were randomly assigned to receive either low-dose aprotinin (1 x 10(6) kallikrein activation units) or placebo. METHODS: The specific renal tubular markers beta-2-microglobulin and beta-N-acetyl-D-glucosaminidase, as well as serum creatinine and blood urea nitrogen, creatinine clearance, sodium excretion, and potassium excretion, were measured to evaluate renal function preoperatively, immediately after the procedure, and 24 hours and 48 hours later. RESULTS: No statistically significant difference was found in any measured renal parameter between the two groups (analysis of variance). Renal dysfunction, defined as an elevation of serum creatinine early postoperatively (> or = 1.5 times the preoperative value), occurred in two patients who received aprotinin and in one patient in the control group. Temporary dialysis (hemodialysis or continuous venovenous hemofiltration) was needed in two patients in the aprotinin group versus one in the control group. Furthermore, patients treated with aprotinin had significantly less total postoperative blood loss (718 +/- 340 ml vs 920 +/- 387 ml, p = 0.04). The aprotinin recipients also had a significantly lower transfusion requirement (p < 0.05). CONCLUSION: This controlled trial of low-dose aprotinin in patients undergoing thoracic aortic operations using profound hypothermic circulatory arrest demonstrated no detectable deleterious effects on renal function; moreover, the use of aprotinin was associated with significantly lower need for transfusion.
Aged↗
Reversal of ventricular dilatation after correction of aortic incompetence: mechanical prosthesis compared with biological procedures.
BACKGROUND: The aim of the study was to compare early differences in reversal of LV dilatation between patients with mechanical prosthesis = group A (n = 51: Carbomedics = 40, Tekna/Edwards = 11) and biological procedures = group B (n = 75: pulmonary autograft = 36, aortic valve repair = 29, homograft = 10). METHODS: Since 1,990,126 consecutive patients younger than 50 years who had surgical correction of isolated aortic incompetence underwent echocardiographic examinations preoperatively, at discharge, and at one-year follow-up. Left-ventricular (LV) diameters were measured (LVEDD, LVESD) and matched to body surface area (LVESDI, LVEDDI and fractional shortening (FS) was calculated. Aortic peak flow velocities were assessed by Doppler technique and gradients were calculated. RESULTS: There were no significant differences preoperatively in aortic incompetence, NYHA classification, LVEDDI, LVESDI, and FS. In group B there was a significant decrease of LVESDI (p < 0.002) and LVEDDI (p < 0.001) but no change in FS at discharge. In group A a significant reduction of FS (p < 0.05) without any significant changes in LV size was observed. No patient died perioperatively or during the first year. At one-year follow-up (complete in 97.6% patients) there were no significant differences in LV diameters but group B had better ventricular function (p < 0.05) resulting in better NYHA classification (p < 0.05). Only group B had normal aortic valve gradients at discharge and at follow-up (A: 25.2 +/- 4.3 vs B: 10.2 +/- 2.4 mmHg). CONCLUSIONS: Normal aortic valve gradients in patients after aortic valve repair or allograft replacement for chronic aortic incompetence lead to early recovery from ventricular dilatation and significantly better ventricular function at discharge. One year postoperatively they had improved ventricular function and NYHA class in comparison with patients in whom a mechanical prosthesis was implanted.
Adult↗
Tissue heat content and distribution during and after cardiopulmonary bypass at 31 degrees C and 27 degrees C.
BACKGROUND: Afterdrop following cardiopulmonary bypass results from redistribution of body heat to inadequately warmed peripheral tissues. However, the distribution of heat between the thermal compartments and the extent to which core-to-peripheral redistribution contributes to post-bypass hypothermia remains unknown. METHODS: Patients were cooled during cardiopulmonary bypass to nasopharyngeal temperatures near 31 degrees C (n=8) or 27 degrees C (n=8) and subsequently rewarmed by the bypass heat exchanger to approximately 37.5 degrees C. A nasopharyngeal probe evaluated core (trunk and head) temperature and heat content. Peripheral compartment (arm and leg) temperature and heat content were estimated using fourth-order regressions and integration over volume from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. RESULTS: In the 31 degrees C group, the average peripheral tissue temperature decreased to 31.9+/-1.4 degrees C (means+/-SD) and subsequently increased to 34+/-1.4 degrees C at the end of bypass. The core-to-peripheral tissue temperature gradient was 3.5+/-1.8 degrees C at the end of rewarming, and the afterdrop was 1.5+/-0.4 degrees C. Total body heat content decreased 231+/-93 kcal. During pump rewarming, the peripheral heat content increased to 7+/-27 kcal below precooling values, whereas the core heat content increased to 94+/-33 kcal above precooling values. Body heat content at the end of rewarming was thus 87+/-42 kcal more than at the onset of cooling. In the 27 degrees C group, the average peripheral tissue temperature decreased to a minimum of 29.8 +/-1.7 degrees C and subsequently increased to 32.8+/-2.1 degrees C at the end of bypass. The core-to-peripheral tissue temperature gradient was 4.6+/-1.9 degrees C at the end of rewarming, and the afterdrop was 2.3+/-0.9 degrees C. Total body heat content decreased 419+/-49 kcal. During pump rewarming, core heat content increased to 66+/-23 kcal above precooling values, whereas peripheral heat content remained 70+/-42 kcal below precooling values. Body heat content at the end of rewarming was thus 4+/-52 kcal less than at the onset of cooling. CONCLUSIONS: Peripheral tissues failed to fully rewarm by the end of bypass in the patients in the 27 degrees C group, and the afterdrop was 2.3+/-0.9 degrees C. Peripheral tissues rewarmed better in the patients in the 31 degrees C group, and the afterdrop was only 1.5+/-0.4 degrees C.
Adult↗