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Biomedical subjects

N de Jonge

Publications and source records attributed to N de Jonge.

At least 19 recordsLinked to original sources
PubMed2001

Exercise performance in patients with end-stage heart failure after implantation of a left ventricular assist device and after heart transplantation: an outlook for permanent assisting?

OBJECTIVES: We sought to study exercise capacity at different points in time after left ventricular assist device (LVAD) implantation and subsequent heart transplantation (HTx). BACKGROUND: The lack of donor organs warrants alternatives for transplantation. METHODS: Repeat treadmill testing with respiratory gas analysis was performed in 15 men with a LVAD. Four groups of data are presented. In group A (n = 10), the exercise capacities at 8 weeks and 12 weeks after LVAD implantation were compared. In group B (n = 15), the data at 12 weeks are presented in more detail. In group C (n = 9), sequential analysis of exercise capacity was performed at 12 weeks after LVAD implantation and at 12 weeks and one year after HTx. In group D, exercise performance one year after HTx in patients with (n = 10) and without (n = 20) a previous assist device was compared. RESULTS: In group A, peak oxygen consumption (Vo2) increased from 21.3+/-3.8 to 24.2+/-4.8 ml/kg body weight per min (p < 0.003), accompanied by a decrease in peak minute ventilation/ carbon dioxide production (VE/Vco2) (39.4+/-10.1 to 36.3+/-8.2; p < 0.03). In group B, peak Vo2 12 weeks after LVAD implantation was 23.0+/-4.4 ml/kg per min. In group C, levels of peak Vo2 12 weeks after LVAD implantation and 12 weeks and one year after HTx were comparable (22.8+/-5.3, 24.6+/-3.3 and 26.2+/-3.8 ml/kg per min, respectively; p = NS). In group D, there appeared to be no difference in percent predicted peak Vo2 in patients with or without a previous LVAD (68+/-13% vs. 74+/-15%; p < 0.37), although, because of the small numbers, the power of this comparison is limited (0.45 to detect a difference of 10%). CONCLUSIONS: Exercise capacity in patients with a LVAD increases over time; 12 weeks after LVAD implantation, Vo2 is comparable to that at 12 weeks and one year after HTx. Previous LVAD implantation does not seem to adversely affect exercise capacity after HTx.

Adult↗
PubMed2001

Histopathologic findings in explanted heart tissue from patients with end-stage idiopathic dilated cardiomyopathy.

Explanted hearts were examined to determine whether specific histopathologic features are present in the myocardium of patients with end-stage idiopathic dilated cardiomyopathy (IDC). Extensive histopathologic examination by light microscopy, electron microscopy and immunohistochemistry revealed marked fibrosis in the hearts of 21 of 37 IDC patients and in 26 of 35 patients with heart diseases of known causes. Reactive (interstitial and perivascular) fibrosis predominated in the IDC hearts, whereas both reparative (replacement) fibrosis and reactive fibrosis were found in the comparison group. Endocardial fibroelastosis was found in nine patients with IDC and in 14 patients from the comparison group. Distinct patterns of fibrosis were the sole significant histopathologic difference between myocardial samples from patients with IDC and from those with heart diseases of known causes. The diffuse presence of reactive fibrosis in IDC patients suggests a more generalised dysfunction that affects the composition of the myocardial extracellular matrix.

Adult↗
PubMed2001

No association between IL-10 promoter gene polymorphism and heart failure or rejection following cardiac transplantation.

Expression of interleukin (IL)-10 influences the frequency of rejection events after organ transplantation. Therefore, 70 heart transplant patients were genotyped for three single nucleotide polymorphisms and a microsatellite polymorphism in the promotor region of the IL-10 gene. The promoter region was amplified by polymerase chain reaction and genotyped by a colorometric oligo ligation assay and gene scan analysis, respectively. Patient groups consisted of patients suffering from dilated cardiomyopathy or ischaemic heart disease. Cardiac donors served as control group. No correlation was found between genotypes and heart failure or rejection after heart transplantation. This may indicate that in heart transplantation, the total balance of cytokine production is more important for post-transplant rejection activities than the levels of IL-10 as such.

Gene Expression↗
PubMed2001

Norepinephrine induces action potential prolongation and early afterdepolarizations in ventricular myocytes isolated from human end-stage failing hearts.

AIMS: Congestive heart failure is characterized by high levels of norepinephrine which is considered to be arrhythmogenic. It is unclear whether increased norepinephrine is only a marker of the severity of heart failure or whether it directly triggers ventricular arrhythmias. METHODS AND RESULTS: Ventricular myocytes were isolated from eight explanted hearts of patients with end-stage heart failure (ischaemic or dilated cardiomyopathy). With the whole-cell configuration of the patch-clamp technique the effect of 1 micromol x l(-1)norepinephrine on action potentials and membrane currents was studied. The cells had a membrane capacitance of 256 +/- 25 pF (n = 26) and action potential duration (APD90) during control conditions was 620 +/- 45 ms at 1 Hz (n = 14). Norepinephrine induced action potential prolongation in all cells and early afterdepolarizations in 50% of them. Norepinephrine significantly increased the calcium current but had no effect on the delayed rectifier current, the inward rectifier current or the transient outward current. Norepinephrine also significantly increased the steady-state calcium window-current measured between -40 and 0 mV. CONCLUSIONS: In contrast to many animal species, norepinephrine induces action potential prolongation in ventricular myocytes from human failing hearts, as well as early afterdepolarization, by an increase in both the calcium peak current and window current. Thus norepinephrine seems to be an important arrhythmogenic factor in congestive heart failure.

Action Potentials↗
PubMed2000

Injury current modulates afterdepolarizations in single human ventricular cells.

OBJECTIVE: Injury current (I(injury)) and afterdepolarizations are thought to play an important role in arrhythmias that occur during acute ischemia. However, little is known about the effects of I(injury) on afterdepolarizations. The present study was designed to study the effect of I(injury) on afterdepolarizations and action potentials in single human ventricular cells. METHODS: The patch-clamp technique was used to record action potentials and to apply I(injury) to human ventricular cells. In these cells, early and delayed afterdepolarizations (EADs and DADs) were induced by 1 microM norepinephrine. I(injury) was simulated by coupling cells via a variable coupling resistance to a passive resistance circuit with a potential of 0, -20, or -40 mV, mimicking a depolarized ischemic region. RESULTS: At all potentials, I(injury) induced depolarization of the resting membrane potential and action potential shortening. Flowing from 0 mV, I(injury) induced EADs by itself and aggravated the EADs and DADs that were induced by norepinephrine. Flowing from -40 mV, I(injury) abolished the noradrenaline-induced EADs and DADs. CONCLUSIONS: Our results demonstrate that I(injury) may either prevent or promote the occurrence of afterdepolarizations in human ventricle. The latter holds if conduction is slowed to such an extent that it permits flow of current from depolarized ischemic cells at plateau level to cells in phase 3 or phase 4.

Action Potentials↗
PubMed2000

Additional use of immunostaining for active caspase 3 and cleaved actin and PARP fragments to detect apoptosis in patients with chronic heart failure.

BACKGROUND: Apoptosis might play a role in the pathophysiology of chronic heart failure (CHF). Detection of apoptosis in tissue mostly relies on the terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) method. Recent studies showed, however, that TUNEL-positive cardiomyocytes were not in apoptosis. Therefore, additional methods are warranted. In this study, we tested the specificity of the TUNEL method by additional immunostaining for enzymes and cleaved proteins that are considered specific for apoptosis. METHODS AND RESULTS: We tested 25 myocardial tissue sections from 16 patients with severe CHF (caused by either idiopathic or ischemic cardiomyopathy) for the existence of apoptosis. We compared TUNEL with immunostaining for caspase 3, active caspase 3, cleaved actin, and poly (ADP-ribose) polymerase (PARP). TUNEL-positive myocytes were seen in 68% of the specimens. Immunostaining in myocytes for active caspase 3 and caspase 3 was positive in only a few patients, whereas staining for cleaved actin and PARP was negative in all patients. CONCLUSION: We found variable myocyte labeling with TUNEL in the failing myocardium of patients with CHF and only obtained scarce additional immunohistochemical evidence for myocyte apoptosis with immunostaining for active caspase 3 and caspase 3 and no positive myocytes with immunostaining for cleaved actin or PARP fragments. These findings support the notion that TUNEL-positive cardiomyocytes are not conclusive for the existence of apoptosis.

Actins↗
PubMed1999

[Successful pregnancy after heart transplantation].

A 32-year-old woman underwent heart transplantation after having suffered two myocardial infarctions, the first when parturition was pharmacologically induced, the second during diagnostic catheterization. Three years after the heart transplantation she became pregnant three times. In the first two pregnancies therapeutic abortion was performed because of trisomy-21. The third pregnancy was uneventful until week 36. At that time labour was induced because of signs of pre-ecclampsia. A healthy boy was born with normal physical and psychological development after four years. In pregnancy after heart transplantation teratogenic effects of the medication have not been described. The main problems are hypertension and pre-eclampsia in the mother and prematurity and low birth weight in the newborn. A major problem is the limited life expectancy after heart transplantation due to which a patient will only rarely see his or her child grow up into adulthood.

Adult↗
PubMed1999

Study on microbial persistence in end-stage idiopathic dilated cardiomyopathy.

Microbial persistence may be involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Therefore, we evaluated the role of various cardiopathogenic microorganisms in patients with end-stage IDC. In a previous study, we did not find evidence for the persistence of enterovirus RNA in end-stage IDC. In the present study, we looked for other microorganisms that are frequently associated with heart disease, including cytomegalovirus, hepatitis B virus, hepatitis C virus, Borrelia burgdorferi, Chlamydia species, mycoplasmata, and Toxoplasma gondii. Serology, polymerase chain reaction (PCR) analysis specific for detection of microbial genomic sequences, or both investigations were performed on myocardial samples from 37 patients with end-stage IDC. PCR analysis was performed on multiple myocardial samples per patient. Thirty-nine patients with end-stage heart disease of known cause were included as controls. On the basis of our serological data and PCR analyses, we did not find any evidence that microbial persistence in the heart is involved in the end-stage disease process of IDC.

Adolescent↗
PubMed1999

Autoimmune markers are undetectable in end stage idiopathic dilated cardiomyopathy.

BACKGROUND: Autoreactive humoral and cellular immune responses may be involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Certain human leucocyte antigens (HLA) could also be linked to the development of IDC. AIM: To determine whether various markers of autoimmunity are present in the final phase of the disease, to substantiate the role of an autoimmune process in IDC. METHODS: 37 patients with end stage IDC were studied, together with 39 patients with end stage heart disease of known aetiology who were included for comparison. Multiple myocardial tissue samples from the explanted heart of each patient were evaluated (immuno)histologically. An indirect immunofluorescence assay was used to screen patient serum samples for the presence of heart specific autoantibodies. HLA class I and II frequencies were determined in each group and compared with HLA frequencies from healthy blood donors. RESULTS: Only scanty small mononuclear cell infiltrates were present in myocardial tissue of seven patients with IDC and of 11 patients with heart disease of known cause. The majority of these inflammatory cells were negative for T cell markers. All blood specimens were negative for heart specific autoantibodies and there was no apparent association of IDC with particular HLA phenotypes. CONCLUSIONS: These findings suggest that an active autoimmune process is not involved in the end stage of IDC.

Adolescent↗
PubMed1998

Efficacy and muscle safety of fluvastatin in cyclosporine-treated cardiac and renal transplant recipients: an exercise provocation test.

BACKGROUND: Dyslipidemia is found in the majority of renal and cardiac transplant recipients. Although 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors significantly lower low-density lipoprotein cholesterol (LDL-C) levels, such treatment has been associated with muscle toxicity, especially when used in combination with cyclosporine (CsA). We investigated the efficacy and muscle safety of fluvastatin, a new 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, in CsA-treated transplant recipients. METHODS: The efficacy was determined by measuring the lipid profile before and after 8 weeks of fluvastatin therapy. As parameter for possible muscle damage, the rise in serum levels of the muscle proteins creatine kinase and myoglobin was measured after an exercise provocation test (30 min on a bicycle ergometer at 60% of their maximal work load) before and during fluvastatin therapy. Nineteen CsA-treated renal and cardiac transplant recipients with hypercholesterolemia were selected. RESULTS: After 8 weeks of treatment with a dose of fluvastatin necessary to reduce LDL-C below 3.5 mmol/L (20 mg for 3 and 40 mg for 16 patients), total cholesterol was lowered by 20% and LDL-C by 30%, and HDL2-C was increased by 35% (all P<0.01). The rise in creatine kinase after exercise before and during fluvastatin therapy was, respectively, 40% and 51%, and the rise in myoglobin was 64% and 50%. These rises were not significantly different. Hence, there was no indication for subclinical muscle pathology by fluvastatin use. Fluvastatin was well tolerated, and no adverse effects on liver or kidney function were found. CONCLUSIONS: Fluvastatin can effectively lower LDL-C in CsA-treated renal and cardiac transplant recipients, without demonstrable adverse effects.

Adult↗
PubMed1998

No evidence for persistent enterovirus infection in patients with end-stage idiopathic dilated cardiomyopathy.

Persistence of enteroviruses in heart tissue has been implicated in the etiology of idiopathic dilated cardiomyopathy (IDC). Therefore, we determined the prevalence of enterovirus RNA in heart tissue from patients with end-stage IDC. During heart transplantation, 287 transmural biopsy specimens were aseptically collected from the explanted hearts of 38 patients with IDC and of 39 patients with cardiac failure of known cause. A nested polymerase chain reaction with general specificity for enteroviruses was used to screen for the presence of enterovirus RNA in the heart tissue samples. No enterovirus RNA was detected in any of the 287 heart biopsy specimens. These findings lead to a conclusion that enteroviruses do not persist in heart tissue from patients with end-stage IDC, nor with other heart diseases of known cause.

Adolescent↗
PubMed1996

Functional recovery after human heart transplantation is related to the metabolic condition of the hypothermic donor heart.

BACKGROUND: Although strict selection criteria are being used for the acceptance of human donor hearts for transplantation, problems with respect to functional recovery on reperfusion sometimes still occur. Therefore, evaluation of the viability of a human donor heart before implantation during heart transplantation may be of great value. METHODS AND RESULTS: In the present study, the energy metabolism of 25 excised human donor hearts arrested with St Thomas' Hospital No. 2 cardioplegic solution was evaluated noninvasively by use of 31P magnetic resonance spectroscopy (MRS) before implantation and was correlated with myocardial function measured with thermodilution in heart transplant patients. No significant correlation was observed between the cardiac index of heart transplant patients during the first hours after transplantation and the phosphocreatine/ATP (r = .13, P = .54), inorganic phosphate/ATP (r = .26, P = .21), phosphomonoesters/ATP (r = .02, P = .92), or phosphocreatine/inorganic phosphate (r = .16, P = .44) ratio or the intracellular pH (r = .06, P = .78) at the time of reperfusion. However, 1 week after transplantation, a significant correlation was observed between the cardiac index and the phosphocreatine/ATP (r = .49, P = .01), phosphomonoesters/ATP (r = .45, P = .02), and phosphocreatine/inorganic phosphate (r = .40, P = .05) ratios at the time of reperfusion. In contrast, the inorganic phosphate/ATP (r = .10, P = .63) ratio and pH (r = .31, P = .13) at the time of reperfusion showed a poor correlation with the cardiac index 1 week after transplantation. CONCLUSIONS: Functional recovery after human heart transplantation is related to the metabolic condition of the hypothermic donor heart.

Adolescent↗
PubMed1996

Unexplained high activity of aspartate aminotransferase (EC 2.6.1.1): a case report.

We report a case of unexplained and persistently elevated ASAT activity in serum. This appeared to be due to a macro-enzyme of ASAT, as was demonstrated by protein-A-Sepharose treatment of the serum sample. Although macro-ASAT seems to be clinically irrelevant, unexplained raised ASAT activity without acknowledgement of its macroenzyme nature may lead to unnecessary diagnostic procedures.

Aspartate Aminotransferases↗
PubMed1996

Haemolytic disease of the newborn due to anti-K antibodies.

We describe a case of intrauterine foetal death at 32 weeks gestation with signs of hydrops foetalis without erythroblastosis. The hydrops foetalis appeared to be caused by blood group incompatibility. Irregular antibodies of anti-K specificity were found in the serum of the mother, while the father was positive for the K-antigen. The antibody dependent cell-mediated cytotoxicity (ADCC) test with serum of the mother was positive. This case shows the characteristics of haemolytic disease of the newborn by anti-K. Moreover, it underlines the necessity of both adequate follow-up of individual cases, and screening for irregular antibodies in all pregnancies as well as central registration of screening results.

Adult↗
PubMed1996

Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction.

OBJECTIVES: We sought to investigate the origin of the fractionated electrogram and its relations to abnormal conduction in cardiomyopathic myocardium. BACKGROUND: Patients with dilated cardiomyopathy have a high incidence of ventricular tachycardias. Electrograms recorded in these patients are often fractionated. METHODS: High resolution mapping (200-microM interelectrode distance) of the electrical activity was carried out in 11 superfused papillary muscles and 6 trabeculae from 7 patients who underwent heart transplantation because of dilated cardiomyopathy. Similar measurements were taken in four papillary muscles from dog hearts in which electrical barriers had been artificially made. Ten human preparations were studied histologically. RESULTS: All preparations revealed sites with fractionated electrograms. In three human preparations, activation patterns showed a discernible line of activation block running parallel to the fiber direction. Fractionated electrograms were recorded at sites contiguous to the line of block. In five preparations, fractionated electrograms were recorded at sites where lines of block were not identified. In these preparations, electrical barriers consisted of short stretches of fibrous tissue. In the remaining nine preparations, fractionated electrograms were recorded, both from sites contiguous to distinct obstacles and sites without evidence of a barrier. CONCLUSIONS: Our observations showed that fractionated electrograms recorded in myocardium damaged by cardiomyopathy were due to both distinct, long strands and short stretches of fibrous tissue. Delayed conduction was caused by curvation of activation around the distinct lines of block and by the wavy course of activation between the short barriers. The latter reflects extreme nonuniform anisotropy.

Animals↗