Glycolytic ATP production is not essential for NA(+)-K+ ATPase function and contractile recovery during postischemic reperfusion in isolated rat hearts.
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Adenosine Triphosphate↗
Biomedical subjects
C J van Echteld
Publications and source records attributed to C J van Echteld.
In situ measurements of creatine kinase flux by NMR. The lessons from bioengineered mice.
P-31 nuclear magnetic resonance (NMR) is uniquely suited to measure the kinetics of the phosphoryl-exchange reaction catalyzed by creatine kinase in intact mammalian tissue, especially striated muscle. Recently developed transgenic mouse models of the creatine kinase iso-enzyme system open novel opportunities to assess the functional importance of the individual iso-enzymes and their relative contribution to the total in situ flux through the CK reaction. This chapter reviews the most recent findings from NMR flux measurements on such genetic models of CK function. Findings in intact mouse skeletal and cardiac muscle in vivo are compared to data from purified mitochondrial and cytosolic creatine kinase in vitro. The relevance of findings in transgenic animals for the function of CK in wild-type tissue is described and the perspectives of transgenic techniques in future quantitative studies on the creatine kinase iso-enzyme system are indicated.
Animals↗
Mathematical model of compartmentalized energy transfer: its use for analysis and interpretation of 31P-NMR studies of isolated heart of creatine kinase deficient mice.
A mathematical model of the compartmentalized energy transfer in cardiac cells is described and used for interpretation of novel experimental data obtained by using phosphorus NMR for determination of the energy fluxes in the isolated hearts of transgenic mice with knocked out creatine kinase isoenzymes. These experiments were designed to study the meaning and importance of compartmentation of creatine kinase isoenzymes in the cells in vivo. The model was constructed to describe quantitatively the processes of energy production, transfer, utilization, and feedback between these processes. It describes the production of ATP in mitochondrial matrix space by ATP synthase, use of this ATP for phosphocreatine production in the mitochondrial creatine kinase reaction coupled to the adenine nucleotide translocation, diffusional exchange of metabolites in the cytoplasmic space, and use of phosphocreatine for resynthesis of ATP in the myoplasmic creatine kinase reaction. It accounts also for the recently discovered phenomenon of restricted diffusion of adenine nucleotides through mitochondrial outer membrane porin pores (VDAC). Practically all parameters of the model were determined experimentally. The analysis of energy fluxes between different cellular compartments shows that in all cellular compartments of working heart cells the creatine kinase reaction is far from equilibrium in the systolic phase of the contraction cycle and approaches equilibrium only in cytoplasm and only in the end-diastolic phase of the contraction cycle. Experimental determination of the relationship between energy fluxes by a 31P-NMR saturation transfer method and workload in isolated and perfused heart of transgenic mice deficient in MM isoenzyme of the creatine kinase, MM-/-showed that in the hearts from wild mice, containing all creatine kinase isoenzymes, the energy fluxes determined increased 3-4 times with elevation of the workload. By contrast, in the hearts in which only the mitochondrial creatine kinase was active, the energy fluxes became practically independent of the workload in spite of the preservation of 26% of normal creatine kinase activity. These results cannot be explained on the basis of the conventional near-equilibrium theory of creatine kinase in the cells, which excludes any difference between creatine kinase isoenzymes. However, these apparently paradoxical experimental results are quantitatively described by a mathematical model of the compartmentalized energy transfer based on the steady state kinetics of coupled creatine kinase reactions, compartmentation of creatine kinase isoenzymes in the cells, and the kinetics of ATP production and utilization reactions. The use of this model shows that: (1) in the wild type heart cells a major part of energy is transported out of mitochondria via phosphocreatine, which is used for complete regeneration of ATP locally in the myofibrils--this is the quantitative estimate for PCr pathway; (2) however, in the absence of MM-creatine kinase in the myofibrils in transgenic mice the contraction results in a very rapid rise of ADP in cytoplasmic space, that reverses the mitochondrial creatine kinase reaction in the direction of ATP production. In this way, because of increasing concentrations of cytoplasmic ADP, mitochondrial creatine kinase is switched off functionally due to the absence of its counterpart in PCr pathway, MM-creatine kinase. This may explain why the creatine kinase flux becomes practically independent from the workload in the hearts of transgenic mouse without MM-CK. Thus, the analysis of the results of studies of hearts of creatine kinase-deficient transgenic mice, based on the use of a mathematical model of compartmentalized energy transfer, show that in the PCr pathway of intracellular energy transport two isoenzymes of creatine kinase always function in a coordinated manner out of equilibrium, in the steady state, and disturbances in functioning of one of them inevitably result
Adenosine Triphosphate↗
The dynamic regulation of myocardial oxidative phosphorylation: analysis of the response time of oxygen consumption.
Although usually steady-state fluxes and metabolite levels are assessed for the study of metabolic regulation, much can be learned from studying the transient response during quick changes of an input to the system. To this end we study the transient response of O2 consumption in the heart during steps in heart rate. The time course is characterized by the mean response time of O2 consumption which is the first statistical moment of the impulse response function of the system (for mono-exponential responses equal to the time constant). The time course of O2 uptake during quick changes is measured with O2 electrodes in the arterial perfusate and venous effluent of the heart, but the venous signal is delayed with respect to O2 consumption in the mitochondria due to O2 diffusion and vascular transport. We correct for this transport delay by using the mass balance of O2, with all terms (e.g. O2 consumption and vascular O2 transport) taken as function of time. Integration of this mass balance over the duration of the response yields a relation between the mean transit time for O2 and changes in cardiac O2 content. Experimental data on the response times of venous [O2] during step changes in arterial [O2] or in perfusion flow are used to calculate the transport time between mitochondria and the venous O2 electrode. By subtracting the transport time from the response time measured in the venous outflow the mean response time of mitochondrial O2 consumption (tmito) to the step in heart rate is obtained. In isolated rabbit heart we found that tmito to heart rate steps is 4-12 s at 37 degrees C. This means that oxidative phosphorylation responds to changing ATP hydrolysis with some delay, so that the phosphocreatine levels in the heart must be decreased, at least in the early stages after an increase in cardiac ATP hydrolysis. Changes in ADP and inorganic phosphate (Pi) thus play a role in regulating the dynamic adaptation of oxidative phosphorylation, although most steady state NMR measurements in the heart had suggested that ADP and Pi do not change. Indeed, we found with 31P-NMR spectroscopy that phosphocreatine (PCr) and Pi change in the first seconds after a quick change in ATP hydrolysis, but remarkably they do this significantly faster (time constant approximately 2.5 s) than mitochondrial O2 consumption (time constant 12 s). Although it is quite likely that other factors besides ADP and Pi regulate cardiac oxidative phosphorylation, a fascinating alternative explanation is that the first changes in PCr measured with NMR spectroscopy took exclusively place in or near the myofibrils, and that a metabolic wave must then travel with some delay to the mitochondria to stimulate oxidative phosphorylation. The tmito slows with falling temperature, intracellular acidosis, and sometimes also during reperfusion following ischemia and with decreased mitochondrial aerobic capacity. In conclusion, the study of the dynamic adaptation of cardiac oxidative phosphorylation to demand using the mean response time of cardiac mitochondrial O2 consumption is a very valuable tool to investigate the regulation of cardiac mitochondrial energy metabolism in health and disease.
Adenosine Diphosphate↗
Brain death-induced alterations in myocardial workload and high-energy phosphates: a phosphorus 31 magnetic resonance spectroscopy study in the cat.
BACKGROUND: Hemodynamic deterioration resulting from brain death-induced myocardial left ventricular dysfunction may preclude heart donation. A reduced myocardial high-energy phosphate content, assessed by biopsy specimens, has been suggested to be responsible for this phenomenon. By applying phosphorus 31 magnetic resonance spectroscopy, in vivo myocardial high-energy phosphate metabolism can be studied continuously. METHODS: Twelve cats were sedated, intubated, ventilated, and studied for 240 minutes. Heart rate, arterial blood pressure, and arterial blood gases were monitored. Central venous pressure was kept constant. Myocardial work was expressed as rate-pressure product (RPP=heart rate x systolic arterial blood pressure). After sternotomy a radio frequency surface coil was positioned onto the left ventricle. A parietal trephine hole was drilled, and an inflatable balloon was inserted. The animal was placed into a 4.7 T horizontal 40 cm bore magnet interfaced to a spectrometer. Brain death (n=6) was induced by rapid inflation of the balloon; the six other cats served as a sham-operated control group. 31P spectra were obtained in 30 seconds, with ventilation and arterial blood pressure curve triggering. The phosphocreatine/to/adenosine triphosphate ratio, as an estimator of energy metabolism, was calculated. RESULTS: Brain death was established within 30 seconds after inflation of the balloon. Changes in RPP were characterized by a triphasic profile with a maximum increase from 19.3+/-1.4 x 10(3) to 87.5+/-8.1 x 10(3) mm Hg x min(-1) (p < .0001 vs control group) at 2 minutes after inflation of the balloon. Subsequently, RPP decreased and was normalized at 15 minutes after inflation. The third phase was characterized by hemodynamic deterioration, which became significant at 180 minutes and resulted in mean arterial pressure of 71+/-12 mm Hg (p < .05 vs control group) at the end of the experimental period. RPP deteriorated to 14.6+/-2.0 x 10(3) mm Hg x min(-1) (p < .05 vs control group) at 240 minutes. Because the heart rate remained constant during the third phase, the decrease in RPP was caused by a decrease in systolic arterial blood pressure. The initial phosphocreatine/adenosine triphosphate ratio of 1.65+/-0.16 varied to 1.52+/-0.06 at 2 minutes, and to 1.73 +/-0.17 (all values NS vs control group and vs initial ratio) at 240 minutes. CONCLUSIONS: The energy status of the heart is not affected by brain death. Therefore brain death-induced hemodynamic deterioration is not caused by impaired myocardial high-energy phosphate metabolism.
Adenosine Triphosphate↗
The role of the Na+ channel in the accumulation of intracellular Na+ during myocardial ischemia: consequences for post-ischemic recovery.
To further elucidate the role of the Na+ channel in the ischemic accumulation of intracellular Na+ (Na+i), 200 microM lidocaine was included in the perfusate for 5 min prior to 30 min of ischemia in isolated rat hearts paced at 5 Hz. Na+i and high-energy phosphates were measured, using 23Na-NMR with the shift reagent TmDOTP5- and 31P-NMR, respectively. Control values of phosphocreatine (PCr) and ATP were 14.1 +/- 1.5 mM and 7.7 +/- 0.7 mM, respectively (all data: mean +/- S.D.). During lidocaine perfusion the rate pressure product (RPP) decreased by approximately 50% and Na+i declined from 11.5 +/- 1.5 mM to 9.8 +/- 2.1 mM. During ischemia Na+i in lidocaine hearts rose to 17.9 +/- 2.5 mM v 28.4 +/- 1.7 mM in control hearts (P<0.05). In hearts in which extracellular Ca2+ was lowered prior to ischemia to reach a similar RPP decrease as in lidocaine hearts, Na+i rose to 26.3 +/- 3.0 mM during ischemia (P<0.05 v lidocaine, N.S. v control). Lidocaine did not affect the decline of PCr during ischemia (to 0.5 +/- 0.5 v 0.7 +/- 0.8 mM in lidocaine and control hearts, respectively) but significantly attenuated the initial decrease of pH(i) (6.06 +/- 0.07 v 5.76 +/- 0.04 after 20 min, P<0.01), attenuated the initial decline of ATP (3.3 +/- 1.3 v 1.5 +/- 0.9 mM after 20 min, P<0.05) and delayed the time to onset of contracture. However, at the end of ischemia pH(i) (5.73 +/- 0.04 and 5.78 +/- 0.05) and ATP (1.2 +/- 0.6 and 0.9 +/- 0.8 mM) were not significantly different. At 30 min of reperfusion Na+i was 14.9 +/- 2.6 mM in lidocaine hearts v 20.0 +/- 3.1 mM in controls. PCr (9.6 +/- 2.3 v 4.9 +/- 0.9 mM, P<0.05) and ATP (3.0 +/- 0.6 v 1.8 +/- 0.6 mM) recovered better in lidocaine hearts. Furthermore, developed and end-diastolic pressure recovered better in lidocaine hearts. In conclusion, Na+ influx during ischemia occurs, at least partly, via the Na+ channels, and blocking this channel during ischemia improves post-ischemic functional and metabolic recovery.
Animals↗
Some triggering mechanism, in addition to perfusion-contraction matching, may be essential to initiate hibernation.
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Animals↗
Fluxes through cytosolic and mitochondrial creatine kinase, measured by P-31 NMR.
The kinetic properties of the cytoplasmic and the mitochondrial iso-enzymes of creatine kinase from striated muscle were studied in vitro and in vivo. The creatine kinase (CK) iso-enzyme family has a multi-faceted role in cellular energy metabolism and is characterized by a complex pattern of tissue-specific expression and subcellular distribution. In mammalian tissues, there is always co-expression of at least two different CK isoforms. As a result, previous studies into the role of CK in energy metabolism have not been able to directly differentiate between the individual CK species. Here, we describe experiments which were directed at achieving this goal. First, we studied the kinetic properties of the muscle-specific cytoplasmic and mitochondrial CK isoforms in purified form under in vitro conditions, using a combination of P-31 NMR and spectrophotometry. Secondly, P-31 NMR measurements of the flux through the CK reaction were carried out on intact skeletal and heart muscle from wild-type mice and from transgenic mice, homozygous for a complete deficiency of the muscle-type cytoplasmic CK isoform. Skeletal muscle and heart were compared because they differ strongly in the relative abundance of the CK isoforms. The present data indicate that the kinetic properties of cytoplasmic and mitochondrial CK are substantially different, both in vitro and in vivo. This finding particularly has implications for the interpretation of in vivo studies with P-31 NMR.
Animals↗
Metabolic and functional consequences of successive no-flow and sustained low-flow ischaemia; a 31P MRS study in rat hearts.
Recently, a model of acute hibernation, based on successive no-flow and low-flow ischaemia in the isolated rabbit heart has been described. In the present study this model was used in isolated rat hearts. 31P NMR was used to follow the time course of intracellular pH (pHi) and high-energy phosphates; mechanical activity of the heart was assessed simultaneously. Control hearts were subjected to 180 min of low-flow ischaemia and 60 min of reperfusion (group A). In the acute hibernation group, low-flow was preceded by 5 min of no-flow ischaemia (group B). In group A contracture developed during low-flow. The time to onset of contracture was 51 min (range: 28 to 123 min). In group B, contracture did not occur during low-flow ischaemia (P < 0.01): recovery of left ventricular developed pressure and end-diastolic pressure was significantly better during the first 15 min of reperfusion (P < 0.05). In group A pHi decreased from 7.06 +/- 0.04 to 6.64 +/- 0.14 during the first 30 min of low-flow. After contracture developed in this group two pHi values were measured amounting to 6.33 +/- 0.15 and 6.86 +/- 0.05 at the end of low-flow. At the end of reperfusion pHi was 6.29 +/- 0.05 and 7.09 +/- 0.06. In group B, pHi decreased from 7.08 +/- 0.03 to 6.55 +/- 0.03 during no-flow ischaemia. During low-flow ischaemia, pHi increased to 6.73 +/- 0.05 and remained constant. During reperfusion pHi recovered to 7.06 +/- 0.03. In group A and B phosphocreatine (PCr) levels at the end of low-flow ischaemia amounted to 13 +/- 8% and 26 +/- 6% of pre-ischaemic levels, respectively. During reperfusion, PCr recovery was better in group B: 67 +/- 12% v 23 +/- 11% (P < 0.05). In group A and B, ATP levels at the end of low-flow ischaemia were 5 +/- 10% and 19 +/- 9%, respectively. The rate of ATP depletion during low-flow ischaemia was initially similar in both groups, but between 45 and 90 min ATP depletion still continued in group A, while this had leveled off in group B (P < 0.01). During reperfusion no significant changes in ATP were observed. We propose that increased glucose transport and glycolytic flux are able to maintain ionic homeostasis and diastolic function when low-flow ischaemia is preceded by a short period of no-flow ischaemia.
Animals↗
Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice.
Myotonic dystrophy (DM) is commonly associated with CTG repeat expansions within the gene for DM-protein kinase (DMPK). The effect of altered expression levels of DMPK, which is ubiquitously expressed in all muscle cell lineages during development, was examined by disrupting the endogenous Dmpk gene and overexpressing a normal human DMPK transgene in mice. Nullizygous (-/-) mice showed only inconsistent and minor size changes in head and neck muscle fibres at older age, animals with the highest DMPK transgene expression showed hypertrophic cardiomyopathy and enhanced neonatal mortality. However, both models lack other frequent DM symptoms including the fibre-type dependent atrophy, myotonia, cataract and male-infertility. These results strengthen the contention that simple loss- or gain-of-expression of DMPK is not the only crucial requirement for development of the disease.
Animals↗
On the expected relationship between Gibbs energy of ATP hydrolysis and muscle performance.
Allowing for creatine kinase buffering of changes in adenine nucleotide concentrations, and the known relationship between muscle performance and rate of ATP hydrolysis by myosin, the variation of exerted force with intracellular Gibbs energy of ATP hydrolysis is calculated for voluntary muscle contraction. The resulting relationship is sigmoidal, most of the operating range coinciding with the quasi-linear range around the inflection point. Finger-flexor muscle magnetic resonance spectroscopy data are shown to be in line with this prediction.
Adenosine Diphosphate↗
Quality assessment in in vivo NMR spectroscopy: VI. Multicentre quantification of MRS test signals.
In this paper the results are presented of a joint European quantitative data-analysis study on a series of in vivo NMR time-domain test signals. The purpose of this study was to investigate, whether the quantitative MRS results from the various European biomedical research-centres can be made more comparable and reproducible. From the results of the study it can be concluded that in case of heavily overlapping NMR lines the quantifications should be done by some form of model function fitting and that, whenever possible, prior knowledge on the quantitative parameters should be incorporated into the quantification algorithms.
Magnetic Resonance Spectroscopy↗
Phosphate metabolism of prior eccentrically loaded vastus medialis muscle during exercise in humans.
The possible alteration of metabolism of the m. vastus medialis was investigated during exercise after eccentric loading. Twelve male subjects performed stepping exercise for 25-60 min. One week before and 24 h after stepping they performed concentric leg exercise at stepwise increasing intensity, while power output was measured. During this concentric exercise and recovery therefrom, phosphorous metabolites were also measured in the m. vastus medialis with magnetic resonance spectroscopy. Creatine kinase and myoglobin in blood were measured before and 72 h after stepping. T1 and T2 1H-relaxation times for water were calculated from magnetic resonance images collected 72 h after stepping, and used as measures for oedema. The subjects perceived substantial soreness from 24 to 72 h after stepping. The ratio of inorganic phosphate over phosphocreatine at rest increased from 0.12 +/- 0.02 (before) to 0.19 +/- 0.04 (24 h after stepping) (P < 0.05). Creatine kinase activity was slightly elevated 72 h after stepping (71 [49-812] U L-1 [median, range]; P < 0.05) compared with baseline values (58 [26-409] U L-1), whereas myoglobin concentration was not significantly elevated (15 [8-120] micrograms L-1 compared with 8 [8-41] micrograms L-1). In the eccentrically exercised muscles, T1 and T2 values were not or only slightly higher than in the concentrically exercised contralateral muscles. The relation between power and the ratio of inorganic phosphate over phosphocreatine during concentric exercise, and the recovery data for inorganic phosphate, phosphocreatine and pH did not alter after stepping. These data suggest that quadriceps metabolism during concentric exercise and recovery therefrom is not affected by prior eccentric overload, but it cannot be excluded that metabolism will alter during exercise after more strenuous prior eccentric overload.
Adult↗
Saturation correction in human cardiac 31P MR spectroscopy at 1.5 T.
This study was conducted to verify the validity of using saturation factors obtained from unlocalized 31P spectra containing both chest wall and heart muscle signals for correcting human heart muscle phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP) ratios. Saturation factors and T1 relaxation times were determined from 31P magnetic resonance spectra of human chest wall and heart muscle simultaneously in healthy volunteers using one-dimensional spectroscopic imaging in combination with a two-dimensional ISIS sequence by using adiabatic 180 degrees inversion and adiabatic 90 degrees excitation pulses at 1.5 T. Blood corrected saturation factors for PCr/beta-ATP at a TR of 2.4 s were significantly different in heart muscle and chest wall muscle, 1.30 +/- 0.25 and 1.73 +/- 0.31, respectively (p < 0.05). T1 values for PCr and beta-ATP in heart muscle were 4.28 +/- 0.72 and 2.99 +/- 0.52 and in chest wall muscle 6.82 +/- 1.07 and 3.39 +/- 0.48, respectively. The T1(PCr)/T1(beta-ATP) ratios in chest wall and heart muscle were not identical. The mean PCr/beta-ATP ratios in heart and chest wall muscle of six healthy volunteers were 1.23 +/- 0.17 and 3.71 +/- 0.53, respectively.
Adenosine Triphosphate↗
Changes in phosphorus compounds and water content in skeletal muscle due to eccentric exercise.
The interrelationship of the time courses of soreness and oedema, and of force and phosphorus metabolites after eccentric exercise was studied. Eight male subjects performed 120 maximal eccentric contractions with their left forearm flexors. Soreness, maximal force, flexion and extension elbow angle, and creatine kinase and myoglobin efflux were followed for 96 h after exercise. For equal periods T1 and T2 relaxation times and muscle cross-sectional area were calculated from magnetic resonance images as indications of oedema, and inorganic phosphate (P(i)) and phosphocreatine (PCr) were measured with magnetic resonance spectroscopy. Soreness on extension increased at 1 h (P = 0.043), T1 and T2 (both P = 0.01) and soreness when the arm was pressed (P = 0.028) at 24 h, and muscle cross-sectional area increased at 48 h (P = 0.01) after exercise. Soreness on extension reached a maximum at 48 h, the other four parameters at 72 h. All parameters related to oedema, and soreness, showed an increasing pattern for the period after exercise as a whole, but the largest increase between two points of measurement occurred earlier for soreness than for oedema. Creatine kinase increased significantly from baseline from 24 h onwards (P = 0.017) and myoglobin from 1 h onwards (P = 0.012). The P(i):PCr ratio differed from baseline for the first time 24 h after exercise (P = 0.018), increased to 225%, and then remained on a plateau until 72 h. Maximal isotonic force decreased to 53% at 1 h (P = 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The effect of experimental cryptorchidism on the phosphorus NMR spectrum of the rat testis.
Magnetic resonance (MR) spectroscopy of the cryptorchid rat testis was used to test whether changes in the MR spectra of the rat testis might be a more sensitive indicator of changes in the metabolic status of germ cells in the testis rather than simply the cell types present. Testes of adult Wistar rats before and during 42 days of experimental cryptorchidism were investigated by in-vivo 31P MR spectroscopy. Results were compared to MR studies of the synchronized developing testis. The testicular phosphomonoester/ATP (PM/ATP) ratio was dependent only on the cell types present, and showed the same characteristics for each cell type present in the degenerating testis as in the developing testis. The testicular phosphodiester/ATP (PD/ATP) ratio decreased rapidly when the number of round and elongated spermatids was reduced. Similar effects, although less pronounced, were seen in the developing testis. The pH decreased rapidly after cryptorchidism, and was related inversely to the PM/ATP ratio, which was also observed in the developing testis. This study demonstrates that MR spectroscopy monitors the cell types present in the rat testis rather than its metabolic status.
Adenosine Triphosphate↗
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↗
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↗