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C J van Echteld

Publications and source records attributed to C J van Echteld.

At least 37 records · Page 2Linked to original sources
PubMed1994

31P-MRS and simultaneous quantification of dynamic human quadriceps exercise in a whole body MR scanner.

An ergometer for dynamic quadriceps exercise in a magnetic resonance (MR) scanner is physiologically validated, and its technical aspects are presented. The reproducibility of heart rate (HR), O2 consumption (VO2), and power (P) during two graded exercises on the MR ergometer was good (n = 8). Graded exercises on the MR ergometer and on a cycle ergometer (n = 17) were similar with respect to the regression lines between 1) HR and VO2 and 2) HR and P; also peak P did not differ significantly (280 +/- 37 and 298 +/- 41 W, respectively). Peak HR (171 +/- 14 and 184 +/- 15 beats/min, respectively), peak VO2 (3.00 +/- 0.51 and 3.54 +/- 0.44 l/min, respectively), and the slope of the regression line between P and VO2 were lower for MR exercise (P < 0.01). During quadriceps exercise in an MR scanner (n = 12), peak P was 64-143 W for the right leg, with corresponding inorganic phosphate-to-phosphocreatine ratios of 0.85-7.2. It is concluded that continuous noninvasive assessment of energy metabolism with 31P-MR spectroscopy and quantification of power output can be performed simultaneously during dynamic quadriceps exercise, without major reduction of the spectral resolution or the signal-to-noise ratio, and that exercise on this MR ergometer currently is the best possible approximation of cycling exercise for MR purposes.

Adult↗
PubMed1994

Cardiac high-energy phosphates adapt faster than oxygen consumption to changes in heart rate.

To investigate the dynamic control of cardiac ATP synthesis, we simultaneously determined the time course of mitochondrial oxygen consumption with the time course of changes in high-energy phosphates following steps in cardiac energy demand. Isolated isovolumically contracting rabbit hearts were perfused with Tyrode's solution at 28 degrees C (n = 7) or at 37 degrees C (n = 7). Coronary arterial and venous oxygen tensions were monitored with fast-responding oxygen electrodes. A cyclic pacing protocol in which we applied 64 step changes between two different heart rates was used. This enabled nuclear magnetic resonance measurement of the phosphate metabolites with a time resolution of approximately 2 seconds. Oxygen consumption changed after heart-rate steps with time constants of 14 +/- 1 (mean +/- SEM) seconds at 28 degrees C and 11 +/- 1 seconds at 37 degrees C, which are already corrected for diffusion and vascular transport delays. Doubling of the heart rate resulted in a significant decrease in phosphocreatine (PCr) content (11% at 28 degrees C, 8% at 37 degrees C), which was matched by an increase in inorganic phosphate (P(i)) content, although oxygen supply was shown to be nonlimiting. The time constants for the change of both P(i) and PCr content, approximately 5 seconds at 28 degrees C and 2.5 seconds at 37 degrees C, are significantly smaller than the respective time constants for oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

Oxygen measurement inside an NMR magnet with a catheter electrode.

In this study we show the possibility of continuous oxygen tension measurement inside an NMR magnet without disturbance of simultaneous NMR data acquisition. Our modified Clark-type oxygen electrode has a fast response (2 s) and can be inserted deep into small bore NMR systems thanks to its small diameter (2 mm).

Animals↗
PubMed1993

Experimental design of 31P MRS assessment of human forearm muscle function: restrictions imposed by functional anatomy.

The restrictions imposed by the functional anatomy of the finger flexor muscles on the experimental design of 31P MRS assessment of human forearm muscle function employing surface coil localization and voluntary exercise were investigated. It was found that 31P MRS metabolic data of finger flexor muscle should be correlated with mechanical data of combined flexion of only the ring and little fingers, rather than all four fingers as has been commonly the case in previously reported studies.

Adenosine Triphosphate↗
PubMed1992

The progression of spermatogenesis in the developing rat testis followed by 31P MR spectroscopy.

To evaluate the use of human testicular 31P MR spectroscopy as a diagnostic tool to differentiate between several stages of male infertility, we have studied the testicular levels of several phosphorus containing compounds in the rat in relation to the condition of spermatogenesis and the cell types present in the seminiferous tubules of the testis. During testicular maturation several characteristic changes occur in the 31P MR spectrum of the testis of male Wistar rats. The phosphomonoester/adenosine triphosphate (PM/ATP) ratio shows a decline from 1.61 to 1.02 between the age of 3 and 12 weeks, whereas the phosphodiester (PD)/ATP ratio increases from 0 to 0.72. The testicular pH increases in the same time from 7.06 to 7.32. Testicular MR data obtained after 12 weeks of age onward do not show significant change anymore. The high PM/ATP ratio is associated by a relative high amount of proliferating spermatogonia and spermatocytes during meiosis in the testis, whereas the PD peak seems to be correlated with the release and maintenance of spermatozoa. The MR spectra show a specific fingerprint in all developmental stages of the rat testis as a result of the different cell types in the testis.

Adenosine Triphosphate↗
PubMed1992

Postischaemic metabolic and functional recovery of rat heart after transient reperfusion with various low Ca2+ concentrations.

OBJECTIVE: The effects of transient low Ca2+ reperfusion after ischaemia on metabolic and functional recovery were studied in isolated rat hearts. METHODS: 31P nuclear magnetic resonance (NMR) was used to monitor creatine phosphate, ATP, intracellular inorganic phosphate (Pi), and intracellular pH during control perfusion (15 min), total ischaemia (30 min), and reperfusion (30 min). During early reperfusion (0-10 min) perfusate [Ca2+] amounted to 1.3 (control group), 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, or 0.7 mmol.litre-1. During late reperfusion (10-30 min) perfusate [Ca2+] was 1.3 mmol.litre-1. Isolated rat hearts were used and perfused according to Langendorff. RESULTS: Recovery of creatine phosphate during early reperfusion was partly abolished during late reperfusion in the 0.1-0.4 mmol.litre-1 groups (p < 0.01). In the 0.1 mmol.litre-1 group creatine phosphate content after 30 min reperfusion was lower (p < 0.05) than in the control group. Recovery of ATP during early reperfusion in the 0.3 mmol.litre-1 group was better than in the control group (p < 0.01). After 30 min reperfusion ATP recovery was better in the 0.3 mmol.litre-1 group (p < 0.01) and worse in the 0.1 mmol.litre-1 group (p = 0.05) than in the control group. Decline of Pi during early reperfusion was more pronounced in the 0.2 and 0.3 mmol.litre-1 groups (p < 0.01) and in the 0.5 and 0.6 mmol.litre-1 groups (p < 0.05) than in the control group. In the 0.3 and 0.4 mmol.litre-1 groups, Pi after 30 min reperfusion was higher (p < 0.05) than after 10 min reperfusion. After 30 min reperfusion left ventricular developed pressure, measured with an intraventricular balloon, was lower in the 0.1 mmol.litre-1 group (p < 0.01) than in the control group. CONCLUSIONS: The data show that under the experimental conditions used successive postischaemic reperfusion with 0.1 and 1.3 mmol.litre-1 Ca2+ resulted in poorer metabolic and functional recovery of the hearts than continuous reperfusion with 1.3 mmol.litre-1 Ca2+. Postischaemic reperfusion with 0.1 mmol.litre-1 Ca2+ may predispose the heart to a mild calcium paradox. Successive reperfusion with 0.3 and 1.3 mmol.litre-1 Ca2+ was optimal in terms of ATP recovery but did not result in an increased recovery of left ventricular developed pressure.

Adenosine Triphosphate↗
PubMed1992

Possible mechanisms of the protective effect of pretreatment with anipamil in ischemic-reperfused isolated rat hearts.

Rats were given anipamil (5 mg/kg) or glucose, intraperitoneally twice daily for 5 days. During this period the mean arterial blood pressure and heart rate were measured daily. The heart was then isolated and perfused. Energy metabolism and intracellular pH were monitored by 31P nuclear magnetic resonance spectroscopy during 30 minutes of ischemia followed by 30 minutes of reperfusion, with a simultaneous isovolumetric measurement of left ventricular contraction. Myocardial norepinephrine and glycogen were assayed immediately after excision of the heart, after 15 minutes oxygenated perfusion, at the end of ischemia and at the end of reperfusion. Metabolic and functional recovery during reperfusion were significantly better in hearts pretreated with anipamil (p less than 0.0005 vs controls). However, protection was not preceded by an effect on mean arterial pressure or heart rate in vivo, or a negative inotropic effect during control perfusion of the isolated hearts. There was no energy sparing effect during ischemia; but intracellular pH during ischemia stabilized at a higher level (p less than 0.0005 vs controls). Myocardial norepinephrine and glycogen stores were not decreased by pretreatment with anipamil, and their release or degradation due to ischemia and reperfusion were also not different from controls. Commonly known mechanisms of myocardial protection by calcium antagonists fail to explain the protection by pretreatment with anipamil as observed in our experiments, and alternative mechanisms are to be considered.

Animals↗
PubMed1991

Chronic cardiotoxicity of adriamycin studied in a rat model by 31P NMR.

Adriamycin induced cardiotoxicity is, among other factors, characterized by an impairment of mitochondrial function and altered energy metabolism. The possible merits of 31P NMR in timely detection of this cardiotoxicity were studied in perfused hearts of chronically treated rats after cumulative doses of 6, 8, 10, 12 and 13 mg adriamycin/kg body wt and compared to histological evaluation. After high cumulative doses the Phosphocreatine (PCr)/ATP ratio was significantly decreased in the hearts of treated animals, compared to the control animals (1.65 +/- 0.13 vs. 2.47 +/- 0.36 (p less than 0.001) at 12 mg/kg and 1.92 +/- 0.22 vs. 2.37 +/- 0.15 (p less than 0.01) at 13 mg/kg adriamycin, respectively). This decrease coincides with a sudden increase in the histological score from 2.0 at 10 mg/kg to 8.0 at 12 mg/kg adriamycin on a scale of 10.0. The Pi/PCr ratio, coronary flow and rate pressure product (RPP) of the isolated hearts of treated animals were not significantly different from controls. When heart rates were increased, parallel changes in PCr/ATP ratio, Pi/PCr ratio, RPP and coronary flow were observed in both control and treated groups, except for the 12 mg/kg adriamycin group in which pacing failed to increase RPP. In addition, in this group the Pi/PCr ratio at higher heart rates was significantly increased (p less than 0.001) compared to controls. At 13 mg/kg similar effects were observed but less pronounced. The decreased PCr/ATP ratio may indicate an increased ADP concentration and altered regulation of energy metabolism. Differences between control and treated groups in RPP and Pi/PCr ratio during pacing may also be related to cardiotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Intracellular sodium during ischemia and calcium-free perfusion: a 23Na NMR study.

Accumulation of sodium-ions (Na+) in myocardial cells during both ischemia and calcium (Ca2+)-free perfusion has been suggested to play an important role in the damage occurring during subsequent reperfusion and calcium repletion, respectively. We have used 23Na NMR spectroscopy in combination with shift reagents to determine intracellular Na(+)-concentration [( Na+]i) in isolated rat hearts during either control perfusion followed by ischemia and reperfusion, or during control perfusion, Ca(2+)-free perfusion and subsequent ischemia. [Na+]i during control perfusion was found to be 10.5 +/- 0.6 mmol/l. During 30 min of ischemia [Na+]i rose substantially to 25.0 +/- 3.2 mmol/l. During 15 min of reperfusion [Na+]i initially decreased, but leveled off after approximately 3 min and was 17.9 +/- 3.7 mmol/l at the end of the reperfusion period. Most surprisingly, however, no significant increase of [Na+]i was observed during 30 min of Ca(2+)-free perfusion, although severe calcium paradox damage was shown to occur under the used conditions, when calcium was readmitted to the heart. The absence of a rise of [Na+]i during Ca(2+)-free perfusion was substantiated when during subsequent ischemia a similar rise of [Na+]i was observed as during ischemia without previous Ca(2+)-depletion. We conclude that an increased [Na+]i during Ca(2+)-depletion is not a prerequisite for the calcium paradox to occur, but that increased [Na+]i during ischemia may influence the subsequent reperfusion damage through Na(+)-Ca2+ exchange.

Animals↗
PubMed1991

Characterization of the testicular cell types present in the rat by in vivo 31P magnetic resonance spectroscopy.

Testes of vitamin A-deficient Wistar rats before and after vitamin A replacement, of rats irradiated in utero, and of control rats were investigated by in vivo 31P magnetic resonance (MR) spectroscopy. The testicular phosphomonoester/ATP (PM/ATP) ratio ranged from 0.79 +/- 0.05 for testes that contained only interstitial tissue and Sertoli cells to 1.64 +/- 0.04 for testes in which spermatocytes were the most advanced cell types present. When new generations of spermatids entered the seminiferous epithelium, this ratio decreased. The testicular phosphodiester/ATP (PD/ATP) ratio amounted to 0.16 +/- 0.06 for testes in which Sertoli cells, spermatogonia, or spermatocytes were the most advanced cell type present. When new generations of spermatids entered the seminiferous epithelium, the PD/ATP ratio rapidly increased and finally reached a value of 0.71 +/- 0.06 for fully developed testes. Taken together, specific patterns of the PM/ATP ratio, the PD/ATP ratio, and pH were obtained that were correlated to the presence of spermatogonia, spermatocytes, round spermatids, and elongated spermatids or to the absence of spermatogenic cells. Hence, a good impression of the status of the seminiferous epithelium in the rat can be obtained by in vivo 31P MR spectroscopy.

Adenosine Triphosphate↗
PubMed1991

Effects of dextromethorphan on rat brain during ischemia and reperfusion assessed by magnetic resonance spectroscopy.

Using proton and phosphorus magnetic resonance spectroscopy, we evaluated the metabolic effects of preischemic administration of the N-methyl-D-aspartate antagonist dextromethorphan (50 mg/kg i.p.) during global forebrain ischemia and subsequent reperfusion in rats. Dextromethorphan-treated animals (n = 10) showed less lactate formation during ischemia than untreated animals (n = 11, p less than 0.001). During reperfusion, the lactate level in the treated group was reduced (p less than 0.05). Tissue pH declined less in the treated group during ischemia (p less than 0.01). There was no difference in the phosphocreatine/inorganic phosphate peak height ratio between groups. During ischemia, the N-acetylaspartate resonance peaks decreased in both groups. Histologic damage assessed in the hippocampal CA1 region 7 days after the ischemic insult was more severe in the untreated group (p less than 0.05). There was a significant correlation between end-ischemic tissue pH and hippocampal damage (r = -0.73, p less than 0.05). In the dextromethorphan-treated animals, 90% of the rats survived compared with 47% of the untreated animals (p less than 0.05). These results support findings in previous studies that dextromethorphan attenuates ischemic damage.

Animals↗
PubMed1990

31P NMR study of cisplatin- and doxorubicin-induced changes in tumour metabolism in rats with a cisplatin-sensitive or -resistant immunocytoma.

The response of tumours to treatment with the cytostatic drugs cisplatin (CDDP) or doxorubicin (DXR) was followed in vivo by 31P NMR spectroscopy. A CDDP-sensitive parent line (IgM-I) and a CDDP-resistant subline (IgM/CDDP) of the IgM-immunocytoma grown s.c. on LOU/M WsL rats were used. Animals from both tumour groups (n = 33) were divided into 3 subgroups: CDDP-treated (1 mg/kg), DXR-treated (10 mg/kg) and control. In 3 out of the 4 treated subgroups where the tumours regressed to less than one half of the initial size, 31P NMR spectroscopy revealed alkaline shifts of 0.31-0.41 pH units at day 4, while the ratio of nucleoside triphosphate to Pi in the tumours, increased continuously to 250-435%. Following CDDP treatment, the 31P NMR spectra of the non-responding IgM/CDDP tumours showed a similar pH increase (0.37 units). The ratio of NTP/Pi showed a temporary decrease to 63 +/- 14% SEM at day 1, which was followed by a recovery to 130 +/- 12% at day 2 and 119 +/- 15% at day 4. The control tumours showed no change in pH and a gradual decrease in the ratio of NTP/Pi. In DXR-treated rats the concentrations of DXR in the immunocytoma tumour and its subline were similar, but in the CDDP-treated rats the IgM-I tumours contained significantly higher levels of platinum than the IgM/CDDP tumours, both measured at 3 and 4 days after administration. The continuous increase in NTP/Pi ratio observed in the responding tumours, is a phenomenon characteristic of tumour regression, while the early temporary decrease in tumour NTP/Pi ratio could be associated with resistance to CDDP. Whether the reported response-specific spectral change applies to other tumour types and other treatment regimens remains to be established.

Animals↗
PubMed1989

Intracellular free magnesium and phosphorylated metabolites in hexokinase- and pyruvate kinase-deficient red cells measured using 31P-NMR spectroscopy.

The erythrocyte metabolism of two patients with nonspherocytic hemolytic anemia caused by a hexokinase deficiency, and a pyruvate kinase deficiency, respectively, were studied with NMR. The complexing of ATP and 2,3-diphosphoglycerate (2,3-DPG) with Mg2+ and hemoglobin (Hb) was determined using 31P-NMR on oxygenated and deoxygenated cells to investigate the influences of these enzyme defects on intracellular magnesium distribution and on Hb oxygen dissociation. In the pyruvate kinase-deficient red blood cells, the 2,3-DPG concentration was almost twice the normal value and the ATP concentration was near the lower limit of the normal range. In the hexokinase-deficient red cell population, the predominance of young cells masked the deficiency. Therefore, reticulocyte control cells were included in this study. In the oxygenated pyruvate kinase-deficient cells, the fraction of ATP that is complexed to magnesium as well as the free Mg2+ concentration were normal, despite the abnormal concentration of 2,3-DPG. In the deoxygenated cells the free Mg2+ concentration was lower than in normal cells. The fraction of Hb complexed with 2,3-DPG was higher than normal in both oxygenated and deoxygenated pyruvate kinase-deficient cells, in accordance with the high p50 of the oxygen-hemoglobin dissociation curve. In hexokinase-deficient cells, two major abnormalities are found: when the cells were deoxygenated, the concentration of ATP and 2,3-DPG fell. This was not observed for any other sample and could, therefore, be a consequence of the hexokinase deficiency. Despite almost normal levels of magnesium-binding metabolites, the free Mg2+ concentration in oxygenated and deoxygenated cels is much lower than in normal cells. This could be a cell-age-related phenomenon, since lower free Mg2+ concentrations were also found in reticulocyte control cells.

2,3-Diphosphoglycerate↗
PubMed1989

Erythrocyte Na+/K+ ATPase activity measured with 23Na NMR.

A 23Na NMR assay for measurement of erythrocyte Na+/K+ ATPase activity is presented. Using the nonpermeant shift reagent dysprosium tripolyphosphate the signals of intra- and extracellular sodium are separated, enabling measurement of sodium fluxes nondestructively, without the need to physically separate the cells from their environment. By increasing membrane permeability with nystatin we have shown that the assay allows the detection of differences in membrane permeability. With low doses of nystatin the ouabain-sensitive sodium flux increased more than twofold. With high doses of nystatin the Na+/K+ pump could not prevent an almost total equilibration of intra- and extracellular sodium. All sodium that entered the cells remained NMR visible, proving that sodium influx can be measured quantitatively. 31P NMR spectra taken before and after the assay revealed a slight acidification of the cells and no significant change in ATP concentration. No evidence of Dy3+ entering the cell was observed.

Cell Membrane Permeability↗
PubMed1989

31P NMR study of the impact of dietary manipulation on tumor metabolism and response to methotrexate.

The effects of nutritional manipulation and subsequent chemotherapeutic treatment upon growth and metabolism of a transplanted rat rhabdomyosarcoma were investigated by in vivo 31P NMR spectroscopy. Nutritional manipulation was accomplished by administration of a protein deprived diet containing no protein and 75.5% glucose. After 5 days the protein deprived rats (PD rats) were nutritionally replenished with a normal protein diet containing 27% protein and 47.3% glucose. Twenty-four hours after nutritional replenishment the PD rats and continuously well-fed controls (NP rats) received methotrexate (MTX, 30 mg/kg, i.p.). 31P NMR spectroscopy of the tumors 24 h after MTX administration showed a decreased ratio of nucleoside triphosphates to inorganic phosphate (referred to as 'ATP/Pi ratio') in PD rats in contrast to an unchanged ATP/Pi ratio in the NP controls. At the time of MTX administration the PD rats had a significantly lower tumor pH than the NP group (6.75 +/- 0.03 [SEM] vs 6.95 +/- 0.04; p less than 0.02). Tumor response in the PD group was significantly (p less than 0.01) enhanced compared to the NP group. These findings indicate that a period of dietary protein deprivation combined with a high glucose load and followed by nutritional replenishment impairs tumor metabolism. The altered metabolic status is expressed by acidification of the tumor and distinct changes in ATP/Pi ratio and appears to relate to an enhanced susceptibility to MTX chemotherapy.

Animals↗
PubMed1989

Intracellular magnesium during myocardial ischemia and reperfusion: possible consequences for postischemic recovery.

Magnesium (Mg2+) is an important regulator of cell energy metabolism, since only MgATP can serve as a substrate for ATP utilizing processes. We used 31P NMR spectroscopy to determine the complexation of ATP with Mg2+ and intracellular free Mg2+ (Mgf) in isolated rat hearts during control perfusion, ischemia and reperfusion. Atomic absorption spectrophotometry was used to determine preischemic and postischemic tissue Mg2+ and release of Mg2+ into the coronary effluent during reperfusion. Mgf increased from 0.60 mmol/l during control perfusion to greater than 6.5 mmol/l after 15 min of ischemia, while we estimated that at that time 6.7 mmol/l Mg2+ had been liberated from ATP. Less than 2% of cellular Mg2+ was released to the effluent during reperfusion after 30 min of ischemia. From spectra obtained during reperfusion the fraction of ATP that was bound to Mg2+ was calculated to be approximately 96% (compared to 94% during control perfusion), indicating that intracellular Mg2+ did not limit the metabolic use of the newly produced ATP. Mgf remained elevated during reperfusion (0.85 mmol/l). We conclude that intracellular Mg2+ deficiency due to leakage of Mg2+ to the extracellular space does not play a role in the poor postischemic recovery in this isolated rat heart model. Nevertheless, high Mg2+ prior to ischemia or during reperfusion may well be protective, due to interactions of Mg2+ with the sarcolemma or intracellular sites, affecting Ca2+,K+ and Na+ distribution and fluxes.

Adenosine Triphosphate↗
PubMed1988

Distribution of phosphorylated metabolites and magnesium in the red cells of a patient with hyperactive pyruvate kinase.

The intracellular distribution of adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) was studied in the red cells of a patient with a "high-ATP syndrome" by using 31P nuclear magnetic resonance. In this patient, red cell ATP was increased 2.5-fold, whereas 2,3-DPG was decreased fourfold due to the presence of a hyperactive pyruvate kinase. In oxygenated red cells, these abnormal concentrations were reflected to the same extent in all complexes in which ATP and 2,3-DPG take part. The diminished amount of 2,3-DPG bound to hemoglobin was almost completely replaced by ATP-hemoglobin complexes. Therefore, free hemoglobin was only slightly increased. In deoxygenated cells, the relative distribution of ATP and 2,3-DPG complexes was significantly disturbed. The main difference was a shift in the ratio of magnesium ATP (MgATP) over the ATP-hemoglobin complex; 74% of total ATP was complexed to hemoglobin (45% in normal cells), whereas the concentration of MgATP was only slightly increased with respect to normal. The shortage in 2,3-DPG bound to hemoglobin could partially be replenished by an increase in hemoglobin (Mg) ATP complexes. Therefore, the amount of uncomplexed hemoglobin raised from 15% in normal cells to 38% in the patient's cells. As a result, the oxygen-dissociation curve was only moderately shifted to the left. It is concluded that the regulatory role of 2,3-DPG in oxygen transport is taken over in part by (Mg) ATP in this patient. In both aerobic and anaerobic cells, the increase in magnesium bound to ATP, either free or bound to hemoglobin, exceeds the decrease in 2,3-DPG Mg complex. In spite of this, the amount of intracellular free Mg++ was normal or slightly lowered. This suggests the presence of a compensatory mechanism by which the amount of total cellular magnesium could be increased.

2,3-Diphosphoglycerate↗