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C J van Echteld

Publications and source records attributed to C J van Echteld.

51 records · Page 3Linked to original sources
PubMed1987

Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity.

In vivo 31P-NMR was used to measure the effects of the anti-tumor drug adriamycin on the energy metabolism of rat heart. The exclusive acquisition of NMR signal from cardiac muscle was assured by positioning a solenoidal radio-frequency NMR coil around the heart. Appropriate control experiments verified that 31P-NMR spectra solely originated from this organ. Acute effects occurring shortly after adriamycin administration are expressed in 31P spectra as a dose-dependent decline in the cardiac levels of phosphocreatine, after which stabilization at a new steady-state level occurs. These acute effects of a single dose are complete in 30-60 min and no significant further changes take place within 150 min after drug introduction. Longer-term effects of single high doses and of multiple lower doses were measured up to a week after the initiation of treatment. It seemed that at a total dose of 20 mg/kg, drug-induced interference with cardiac energy metabolism was more pronounced than at the same dose in the acute phase. These 31P-NMR data demonstrate that adriamycin treatment is accompanied by a decrease of the cardiac phosphocreatine/ATP ratio which might be an expression of the well-established cardiotoxicity of the drug.

Adenosine Triphosphate↗
PubMed1987

31P NMR study of intracellular pH during the calcium paradox.

Reperfusion of an isolated mammalian heart with a calcium-containing solution after a brief calcium-free perfusion results in irreversible cell damage: the calcium paradox. It has been suggested that acidification of the cytosol, as a result of hydrolysis of ATP and accumulation of calcium by mitochondria, is an important factor in the development of the calcium paradox. Phosphorus nuclear magnetic resonance (31P NMR) spectroscopy was used to investigate the course of intracellular pH during the calcium paradox in isolated rabbit heart at 37 degrees C. Intracellular pH was measured from the chemical shift of the intracellular inorganic phosphate (Pi) peak. During control perfusion and the subsequent calcium-free period intracellular pH amounted to 7.1. After induction of the calcium paradox by readmitting calcium to the perfusion fluid, intracellular pH amounted to 7.0. It is concluded that acidification of the cytosol does not play a causal role in the development of the calcium paradox.

Animals↗
PubMed1983

Protective effect of nifedipine in myocardial ischemia assessed by phosphorus-31 nuclear magnetic resonance.

Calcium antagonists may protect the myocardium against the consequences of ischemia. Phosphorus-31 nuclear magnetic resonance (31P NMR) was used to study the effect of nifedipine on intracellular acidosis and high energy phosphate depletion during global ischemia. Isolated rat hearts were paced (300 beats/min), perfused with a modified Tyrode solution for 30 min, made totally ischemic for 30 min (37 degrees C) and then reperfused for 30 min. When required, nifedipine (1 mg/l) was added to the perfusion fluid 10 min before ischemia. During ischemia intracellular pH fell from 7.11 +/- 0.03 (mean +/- S.E.M.) to 5.88 +/- 0.04 in the untreated hearts (n = 6), and from 7.11 +/- 0.03 to 5.95 +/- 0.02 in the treated hearts (n = 6). During the first 20 min of ischemia, intracellular pH was significantly higher in the treated than in the untreated hearts (P less than 0.001). Myocardial creatine phosphate (CP) content was depleted after 15 min of ischemia in the untreated hearts, and after 20 min of ischemia in the hearts treated with nifedipine. Myocardial adenosine triphosphate (ATP) content was depleted after 20 min of ischemia in the untreated hearts; ATP content in hearts that received nifedipine amounted to 23.5 +/- 6.2% of control after 30 min of ischemia. In contrast with the untreated hearts, the nifedipine-treated hearts showed a rapid recovery of CP content during reperfusion. The results indicate that nifedipine protects the myocardium against the metabolic consequences of ischemia and reperfusion.

Adenosine Triphosphate↗
PubMed1981

Ca2+-induced changes in the barrier properties of cardiolipin/phosphatidylcholine bilayers.

(1) A selective increase in permeability is induced in cardiolipin/phosphatidylcholine bilayers at Ca2+ concentrations of 1--3 mM. At higher concentrations of Ca2+ the permeability barrier is completely destroyed. (2) The selective increase in permeability is correlated with the formation of lipid particles visualized by freeze-fracture electron microscopy and an isotropic signal in 31P-NMR spectra. (3) Lowering the Ca2+ concentration shows reduction in permeability but the formation of the lipid particles is a non-reversible process. (4) At higher Ca2+ concentrations, 31P-NMR spectra and freeze-fracture results indicate the formation of the hexagonal phase, explaining the disappearance of the permeability barrier.

Calcium↗
PubMed1981

Lipidic particles.

A new type of lipid organization is observed in mixtures of phosphatidylcholine with cardiolipin in the presence of Ca++, monoglucosyldiglyceride and phosphatidylethanolamine (in the presence of cholesterol). This phase is characterized by an isotropic 31P NMR signal and is visualized by freeze fracturing as particles and pits on the fracture faces of the lipid bilayer. As the most favourable model for this phase we propose the inverted micelle sandwiched in between the two monolayers of the lipid bilayer. It will be shown that such particles and pits appear on the fusion site during fusion of unilamellar vesicles of an equimolar mixture of phosphatidylcholine and cardiolipin in the presence of Ca++.

Calcium↗
PubMed1980

13C-NMR detection of lipid polymorphism in model and biological membranes.

1. The application of the 13C-NMR technique to the study of lipid polymorphism is described for various model and biological membranes. 2. The 13-C-NMR line-width of various resonances of the lipid molecule and sensitive to the bilayer in equilibrium hexagonal and the bilayer in equilibrium 'isotropic' phase transition. The latter transition in some cases is accompanied by the occurrence of lipidic particles as detected by freeze-fracturing. Thus, specific 13C-labeling experiments allow the study of the individual phase behaviour of lipids in mixed lipid systems. 3. In diet experiments using rats, the choline group of phosphatidylcholine present in erythrocyte, endoplasmic and sarcoplasmic reticulum membranes could be specifically 13C-labeled. The 13C line-widths of the resonance from the erythrocyte are typical for a lamellar arrangement of the membrane lipids. In strong contrast, the line-width observed at 37 degree C for the endoplasmic and sarcoplasmic reticulum membranes is much smaller, typical of the isotropic phases observed in model membranes. In isolated rat liver microsomes and liver slices, the 13C line-width is strongly temperature dependent. At lower temperatures the line-widths strongly increase towards values typical of lipids in a bilayer structure.

Animals↗
PubMed1980

The lipidic particle as an intermediate structure in membrane fusion processes and bilayer to hexagonal HII transitions.

Small unilamellar vesicles comprised of a mixture of phosphatidylethanolamine/phosphatidylcholine/cholesterol (3 : 1 : 2) fuse to form large multilamellar vesicles on increasing the temperature from 0 to 50 degrees C. This event is associated with the appearance of lipidic particles at the fusion sites, consistent with a role as intermediary structures during the fusion process. Further, for phosphatidylcholine/cardiolipin (1 : 1) liposomes in the presence of Mn2+ a direct relationship between lipidic particles and the hexagonal (HII) phase is demonstrated which suggests that lipidic particles can also occur as intermediaries between bilayer and hexagonal (HII) structures.

Cell Fusion↗
PubMed1980

Association of lysophosphatidylcholine with fatty acids in aqueous phase to form bilayers.

Lysophospholipids have been implicated in a variety of physiological process. In vivo lysophospholipids are invariably produced with fatty acids as the product of hydrolysis by phospholipase A2 (ref. 2). Therefore, it is of considerable interest to examine the properties of the mixture of these lipids in aqueous suspensions. Results presented here demonstrate that a mixture of fatty acid and lysophosphatidylcholine forms a bilayer type of organisation even though the individual components form micelles when dispersed in an aqueous phase.

Chemical Phenomena↗
PubMed1980

Barrier characteristics of membrane model systems containing unsaturated phosphatidylethanolamines.

The barrier characteristics of membrane model systems containing unsaturated phosphatidylethanolamines have been investigated. (1) At increasing temperatures 18:1c/18:lc-phosphatidylethanolamine liposomes lose their permeability barrier for K+ as a consequence of the transition from a lamellar to a hexagonal orientation as detected by 31P-NMR and freeze-fracturing electron microscopy. (2) Introduction of 18:1c/18:1c-phosphatidylcholine in the 18:1c/18:1c-phosphatidylethanolamine lipid system stabilizes the bilayer structure and the permeability barrier for K+ and glucose while cholesterol destabilizes. (3) Upon heating of the investigated 18:1c/18:1c-phosphatidylcholine-18:1c/18:1c-phosphatidylethanolamine-(cholesterol) mixtures, structures are formed which give rise to isotropic 31P-NMR signals and which on the basis of freeze-fracture pictures are interpreted as sponge-like structures. Lowering the temperature results in restoration of the barrier function of the lipid structures.

Freeze Fracturing↗
PubMed1979

The occurrence of lipidic particles in lipid bilayers as seen by 31P NMR and freeze-fracture electron-microscopy.

A new type of lipid organization is observed in mixtures of phosphatidyl-choline with cardiolipin (in the presence of Ca2+), monoglycosyldiglyceride and phosphatidylethanolamine (in the presence of cholesterol). This phase is characterised by an isotropic 31P NMR signal and is visualised by freeze-fracturing as particles and pits on the fracture faces of the lipid bilayer. As the most favourable model for this phase we propose the inverted micelle sandwiched in between the two monolayers of the lipid bilayer.

Calcium↗
PubMedDate not supplied

Heterotopic heart transplantation alters high-energy phosphate metabolism irrespective of cardiac allograft rejection.

This study was undertaken to validate the potential of 31P magnetic resonance spectroscopy (MRS) as a noninvasive alternative for transvenous endomyocardial biopsy in detecting cardiac allograft rejection. Donor hearts from either Lewis rats (L) or Brown-Norway rats (BN) were transplanted into the neck of L rats resulting in a non-rejecting group L-L and a rejecting group L-BN. L-L and L-BN rats were serially studied by means of 31P MRS from postoperatine day 1-8. In addition, rejection was confirmed by histology. A similar, marked decrease in phosphocreative/beta- adenosinetriphosphate (PCr/ATP) ratio from day 1-3 was observed in both L-L and L-BN hearts. This ratio levelled off on postoperative day 3 and remained depressed on subsequent postoperative days in both groups, although histology showed an increase in the severity of rejection in L-BN. However, the PCr signal/noise ratio in L-BN started to decrease after day 4, coinciding with the histologic evidence of severe rejection (score IV), whereas in L-L hearts (score 0) this ratio remained unaltered until day 8. Since high-energy phosphate metabolism is affected by the unloaded status of the heterotopically transplanted heart, irrespective of rejection, the PCr/ATP ratio appears not to be a specific marker for the detection of acute rejection in this model. In contrast, the PCr S/N ratio appears to be a specific and sensitive marker of acute rejection, but only in a late, severe stage.

Animals↗
PubMedDate not supplied

A phosphorus-31 nuclear magnetic resonance study of myocardial ATP content during postischemic low calcium reperfusion.

Postischemic reperfusion injury can be modified by transient low calcium (Ca2+) reperfusion, although the data on the optimal [Ca2+] are controversial. High-energy phosphates and contractile function of isolated perfused rat hearts (37 degrees C, 300 beats/min) were studied simultaneously during global ischemia (30 min) and reperfusion (10 min at [Ca2+] = 1.3, 0.05, 0.1, 0.3, 0.5 and 0.7 mmol/l, followed by 20 min at [Ca2+] = 1.3 mmol/l), using phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy. Reperfusion with 1.3 mmol/l Ca2+ after 0.05 or 0.1 mmol/l Ca2+ largely abolished the recovery of ATP obtained during initial low Ca2+ reperfusion (calcium paradox effect). A [Ca2+] of 0.3 mmol/l was sufficiently high to prevent this detrimental effect; at the same time this concentration was sufficiently low to cause a substantial recovery of ATP, which was maintained upon switching to 1.3 mmol/l Ca2+. Recovery of ATP did not correlate with recovery of contractile function.

Adenosine Triphosphate↗