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Circulating leucocyte and lymphocyte subpopulations before and after intensive endurance exercise to exhaustion.

Seventeen healthy cyclists [age 20.8 (SD 4.8) years; body mass 68.3 (SD 7.7) kg; body fat, 11.4 (SD 2.6) %; height, 179.1 (SD 5.9) cm; VO2max, 60.9 (SD 7.4) ml.kg-1.min-1] conducted intensive endurance exercise to exhaustion (stress test, ST) on a cycle ergometer at 110% of their individual anaerobic threshold [Than,individual; exercise intensity, 3.97 (SD 0.6) W.kg-1; duration, 23.9 (SD 8.3) min; maximal lactate concentration, 7.39 (SD 2.59) mmol.l-1]. The distribution of leucocyte subpopulations was measured flow cytometrically: before, immediately after (0), 5 (+5), 30 (+30) and 60 (+60) min after ST. The lymphocytes (0 min) and granulocytes (+60 min) were mainly responsible for the increase of leucocytes. Lymphocytes were significantly lower at +30 and +60 min than before. CD3-CD16/CD56+ (+480%) and CD8(+)-lymphocytes (+211%) increased at 0 min more than the other lymphocyte subpopulations (CD(3+)-cells, +100%; CD(4+)-cells, +56%; CD(19+)-cells, +64%). CD3-CD16/CD(56+)- and CD(8+)-cells also were mainly responsible for the decreased values of lymphocytes at +30 min and +60 min compared to before. At 0 min naive CD(8+)-cells (CD45RA+, CD45RO-) increased more than memory CD(8+)-cells (CD45RA-, CD45RO+). Changes of naive and memory CD(4+)-cells did not differ. All lymphocyte subpopulations, in particular CD(8+)- and CD3-CD16/CD(56+)-cells, decreased rapidly between 0 min and 5 min. We conclude that an intensive endurance exercise to exhaustion causes a mobilisation of lymphocytes, especially of natural killer cells (CD3-CD16/CD56+) and naive, unprimed CD(8+)-cells (CD45RA+, CD45RO-) which may be transported to injured muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Plasticity in corticomotor control of the human tongue musculature induced by tongue-task training.

Transcranial magnetic stimulation (TMS) has been used to assess characteristics of the corticomotor control of the jaw muscles, but less is known about the cortical control of the human tongue and its modification by training. The aim of the present study was to determine the effect of training humans in a novel tongue-protrusion task for 1 week on corticomotor excitability as assessed by changes in electromyographic activity elicited in the tongue musculature by TMS, and in the tongue cortical motor map revealed by TMS. Eleven healthy subjects participated. Stimulus-response curves were generated from the motor evoked potentials (MEPs) recorded in the tongue musculature and, from the first dorsal interosseos (FDI) muscle as a control, at three time periods: at baseline, immediately after the 1-week training period, and at 2-weeks follow-up. In addition, the corticomotor representations of the tongue and FDI muscles were mapped on a 1 x 1 cm scalp grid. The tongue-training task required each subject to protrude the tongue onto a force transducer placed in front of the subject, and consisted of a relax-protrude-hold-relax cycle lasting 12.5 s with 1 N as the target at the hold phase. The subjects repeated this task for 60 min every day for 1 week. All subjects reported moderate levels of fatigue in the tongue during the first training day; however, these subjective reports decreased during the week (ANOVA P<0.001), and the subjects showed a progressive increase in their ability to perform the task successfully ( P<0.001). The threshold for evoking MEPs by TMS in the tongue musculature was significantly decreased after the last training day compared with baseline and the 2-weeks follow-up ( P<0.001). The amplitude of the MEPs in the tongue musculature was significantly increased at higher intensities of TMS after the last training day but returned to baseline values at the 2-weeks follow-up (P = 0.005). No significant effect of the training on MEPs in the FDI was observed (P = 0.493). Analysis of the corticomotor topographic maps revealed a significant ( P<0.05) increase in excitability and, hence, the cortical area from which TMS could evoke MEPs in the tongue, although the center of gravity representation for the tongue or FDI muscles remained stable. The present findings suggest that a specific and reversible plasticity of the corticomotor excitability related to tongue muscle control can be induced when humans learn to perform successfully a novel tongue task.

Adult↗

Patterns of body temperature during feeding in rats under varying ambient temperatures.

Relationships between feeding and body temperature of rats were investigated at three ambient temperatures during the whole light/dark cycle. Basal liver temperature was negatively correlated with ambient temperature. Only at 29 degrees C liver temperature indicated activation of autonomic and locomotory thermoregulatory responses due to heat stress. At 21 degrees C, liver temperature was always higher than skin temperature. Both showed a clear circadian rhythm with higher values during the dark phase. Meal-associated temperature patterns were superimposed on this circadian rhythm. Liver and skin temperatures showed a preprandial and prandial rise. Liver temperature reached an almost similar peak value just above 39 degrees C at the end of a meal, irrespective of meal size and ambient temperatures of 13 degrees C and 21 degrees C. Liver temperature reached this peak about 2 min earlier and dropped sooner than skin temperature. These results indicate a threshold liver temperature at which feeding activity stops. The present study suggests that temperatures do not exceed this value by adaptive autonomic thermoregulatory responses shifting heat flow from core to skin and by stopping all locomotory activities including feeding, thereby avoiding deterioration of vital organs and physiological processes due to hyperthermia.

Animals↗

Converging patterns of uptake and hydraulic redistribution of soil water in contrasting woody vegetation types.

We used concurrent measurements of soil water content and soil water potential (Psi(soil)) to assess the effects of Psi(soil) on uptake and hydraulic redistribution (HR) of soil water by roots during seasonal drought cycles at six sites characterized by differences in the types and amounts of woody vegetation and in climate. The six sites included a semi-arid old-growth ponderosa pine (Pinus ponderosa Dougl. ex P. Laws & C. Laws) forest, a moist old-growth Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) forest, a 24-year-old Douglas-fir forest and three Brazilian savanna sites differing in tree density. At all of the sites, HR was confined largely to the upper 60 cm of soil. There was a common threshold relationship between the relative magnitude of HR and Psi(soil) among the six study sites. Below a threshold Psi(soil) of about -0.4 MPa, overnight recharge of soil water storage increased sharply, and reached a maximum value of 80-90% over a range of Psi(soil) from ~ -1.2 to -1.5 MPa. Although amounts of water hydraulically redistributed to the upper 60 cm of soil were relatively small (0 to 0.4 mm day(-1)), they greatly reduced the rates of seasonal decline in Psi(soil). The effectiveness of HR in delaying soil drying diminished with increasing sapwood area per ground area. The relationship between soil water utilization and Psi(soil) in the 20-60-cm layer was nearly identical for all six sites. Soil water utilization varied with a surrogate measure of rhizosphere conductance in a similar manner at all six sites. The similarities in relationships between Psi(soil) and HR, soil water utilization and relative rhizosphere conductance among the six sites, suggests that, despite probable differences in maximum rooting depth and density, there was a convergence in biophysical controls on soil water utilization and redistribution in the upper soil layers where the density of finer roots is greatest.

Climate↗

Cardiac autonomic regulation after moderate and exhaustive exercises.

The purpose of this study was to investigate the recovery kinetics of cardiac autonomic regulation after acute exercises related to exercise intensity. Firstly, eight healthy subjects performed two kinds of constant load exercises at the work rate corresponding to 20% and 100% of the individual ventilatory threshold (VT) in addition to the exhaustive incremental exercise using a cycle ergometer. Blood pressure (BP) and oxygen uptake (VO2) were measured during 9 to 10 min after the exercises as well as the beat-by-beat recording of R-R intervals. Coarse graining spectral analysis (CGSA) was applied to heart rate variability (HRV) data sets of 5 min before exercise, last 5 min during exercise, and 8 to 10 min after exercise. The low frequency (0-0.15 Hz; LO) and the high frequency (0.15-0.5 Hz: HI) areas under power spectra were calculated for evaluating sympathetic (LO/HI) and vagal (HI) activities. The recovery for 10 min was sufficient to settle both VO2 and BP even after the exhaustion. Comparing to the pre-exercise value, however, HI was still suppressed until 10 min after the 100% VT exercise (522 +/- 300 vs. 122 +/- 63 msec2, p less than 0.05) while it was recovered at 10 min after the 20% VT one (353 +/- 122 vs. 487 +/- 159msec2). Secondly, six healthy subjects performed an incremental cycle exercise until exhaustion. The R-R intervals were monitored beat-by-beat during 30 min after exercise. The CGSA was applied to every five min data set of HRV during recovery phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The off-transient pulmonary oxygen uptake (VO(2)) kinetics following attainment of a particular VO(2) during heavy-intensity exercise in humans.

The oxygen uptake response to moderate-intensity exercise (i.e. < anaerobic threshold (an)) has been characterised with a gain (i.e. response amplitude per increment of work rate) and time constant that do not vary appreciably at different work rates or between the on- and off-transients. Above an, the response becomes more complex with an early component that typically projects to a value that has a gain similar to that of the < an response, but which is supplemented by the addition of a delayed slow kinetic component. We therefore established a constant target VO2 (VO21) for each subject such that with different imposed work rates the contribution to VO21 from the slow phase varied over a wide range. Work rates were chosen so that VO21 was attained at 2-24 min. Five subjects (aged 21-58 years) cycled at four to five different work rates. VO2 was measured breath-by-breath, at VO21 the work rate was abruptly reduced and the subject recovered by cycling unloaded for 15 min. Unlike the on-transient, for which the slow component shows a long delay, the off-transient was best fitted as two simultaneous exponential components. The slower off-transient component had a small amplitude and long time constant, but did not differ significantly among the various tests. The off-transient kinetics for VO2 therefore was independent of the magnitude of the contribution to the slow phase from the on-transient kinetics.

Adult↗

Synthesis and thrombolytic activity of new thienopyrimidinone derivatives.

It has been observed that ticlopidine and clopidogrel show, apart from their delayed antiplatelet properties, an immediate and transient thrombolytic action related to the ability of these thienopyridines to stimulate the secretory function of vascular endothelium. With the objective to construct new molecules with identical thrombolytic potency but at a higher level, we carried out different structural modifications in the thienopyridine chemical molecule to conclude that the presence of a second N atom in the pyridine cycle (yielding pyrimidine moiety) and the presence of an additional cycle fused to the thienyl ring would lead to enhanced thrombolytic effects. Here we report the six-step synthesis of a series of new benzothienopyrimidinone derivatives characterized by this searched for potent thrombolytic activity. The pharmacological assay used anaesthetised Wistar rats with extracorporal circulation in which arterial blood superfused thrombi adhering to a strip of collagen. Weight of thrombi was continuously monitored. Six compounds of the series were much more potent thrombolytic agents than their thienopyridine references: the effective thrombolytic dose that produced 30% of maximum thrombolysis (ED30) was at a range of 8 to 170 microg kg(-1) as compared with ED30 values of 16000 to 20000 microg kg(-1) for clopidogrel and ticlopidine respectively. Especially with the most active compound, this difference in the threshold thrombolytic dose, giving an intensity of action higher by three orders of magnitude, was accompanied by a lengthening of the response. Apart from that these compounds have shown to be synthetic thrombolytics, they certainly deserve further studying.

Animals↗

Pressure relief characteristics in alternating pressure air cushions.

In this study a computerised system was used which continuously measured air pressure, interface pressure and pressure-time cycle characteristics of an alternating pressure air cushion (APAC), and calculated the time the interface pressure remained below three chosen thresholds of 20, 40 and 60 mm Hg. Ten healthy volunteers were used to evaluate the pressure relieving characteristics of four APACs. Results indicated significant differences between products when the threshold periods were analysed, showing some devices were not capable of relieving interface pressures below 20 mm Hg. Though deflation pressure decreased to nearer zero, interface pressure did not follow suit.

Adult↗

Influence of light intensity on plasma melatonin and locomotor activity rhythms in tench.

Melatonin production by the pineal organ is influenced by light intensity, as has been described in most vertebrate species, in which melatonin is considered a synchronizer of circadian rhythms. In tench, strict nocturnal activity rhythms have been described, although the role of melatonin has not been clarified. In this study we investigated daily activity and melatonin rhythms under 12:12 light-dark (LD) conditions with two different light intensities (58.6 and 1091 microW/cm2), and the effect of I h broad spectrum white light pulses of different intensities (3.3, 5.3, 10.5, 1091.4 microW/cm2) applied at middarkness (MD) on nocturnal circulating melatonin. The results showed that plasma melatonin in tench under LD 12:12 and high light conditions displayed rhythmic variation, where values at MD (255.8 +/- 65.9 pg/ml) were higher than at midlight (ML) (70.7 +/- 31.9 pg/ml). Such a difference between MD and ML values was reduced in animals exposed to LD 12: 12 and low light intensity. The application of 1 h light pulses at MD lowered plasma melatonin to 111.6 +/- 3.2 pg/ml (in the 3.3-10.5 microW/cm2 range) and to 61.8 +/- 18.3 pg/ml (with the 1091.4 microW/cm2 light pulse) and totally suppressed nocturnal locomotor activity. These results show that melatonin rhythms persisted in tench exposed to low light intensity although the amplitude of the rhythm is affected. In addition, it was observed that light pulses applied at MD affected plasma melatonin content and locomotor activity. Such a low threshold suggests that the melatonin system is capable of transducing light even under dim conditions, which may be used by this nocturnal fish to synchronize to weak night light signals (e.g., moonlight cycles).

Animals↗

Evaluation of blood lactate elevation as an intensity criterion for exercise training.

We sought to determine whether exercise intensities not elevating blood lactate produce alterations in physiological responses to exercise associated with training. Twenty-seven sedentary young men performed five cycle ergometer training sessions.wk-1 for 5 wk. Training power outputs were randomized to power outputs corresponding to either 80% of the lactic acidosis threshold (LAT), 25% delta or 50% delta (where delta is the difference between LAT and peak VO2 power outputs estimated from incremental exercise tests). Exercise sessions were 30 min for the 50% delta group and were proportionately longer for other groups, so that total work did not vary among groups. Before and after training, subjects exercised for 15 min (or to tolerance) at pretraining 80% LAT, 25% delta, 50% delta, and 75% delta power outputs. Continuous O2 uptake, CO2 output, ventilation and heart rate, and end-exercise blood lactate, norepinephrine, and epinephrine were measured. For the 80% LAT group, posttraining end-exercise values for the 75% delta test were significantly lower for each of these variables. There were similar reductions in each variable in all three training groups; no significant differences among groups were seen. Thus, in healthy subjects exercise which does not elevate blood lactate alters constant power output responses as effectively as exercise which elevates lactate, provided that total training work is the same.

Adult↗

Half sine, monophasic and biphasic transcranial magnetic stimulation of the human motor cortex.

OBJECTIVE: To compare half sine transcranial magnetic stimuli (TMS) with conventional monophasic and biphasic stimuli, measuring resting and active motor threshold, motor evoked potential (MEP) input/output curve, MEP latency, and silent period duration. METHODS: We stimulated the dominant hand representation of the motor cortex in 12 healthy subjects utilising two different MagPro stimulators to generate TMS pulses of distinct monophasic, half sine and biphasic shape with anteriorly or posteriorly directed current flow. RESULTS: The markedly asymmetric monophasic pulse with a posterior current flow in the brain yielded a higher motor threshold, a less steep MEP input/output curve and a longer latency than all other TMS types. Similar but less pronounced results were obtained with a less asymmetric half sine pulses. The biphasic stimuli yielded the lowest motor threshold and a short latency, particularly with the posterior current direction. CONCLUSIONS: The more asymmetric the monophasic pulse, the stronger the difference to biphasic pulses. The 3rd and 4th quarter cycle of the biphasic waveform make it longer than any other waveform studied here and likely contribute to lowering motor threshold, shortening MEP latency and reversing the influence of current direction. SIGNIFICANCE: This systematic comparison of 3 waveforms and two current directions allows a better understanding of the mechanisms of TMS.

Adult↗

First experience with an automatic sensing algorithm in single-lead VDD stimulation.

UNLABELLED: An "Autosensing" algorithm available in SSI(R) and DDR(R) pacemakers automatically adapts the device's sensitivity to changing intracardiac signals. The atrial sensing function of this algorithm was tested for the first time with a VDD pacing system in which large variations of the atrial signal may occur because the atrial electrodes float in the atrial blood pool. METHODS: 15 patients with a VDD pacing system were studied (Unity 292-07, lead 425; Sulzer Intermedics). The atrial sensing threshold was measured, and the atrial sensitivity was programmed with a 2:1 safety margin. The autosensing algorithm and sensitivity profile were temporarily activated, and an ambulatory ECG with continuous marker annotation was recorded. All patients underwent a 30-minute daily life activities protocol. A beat-to-beat analysis of the ambulatory ECG was correlated with the changes in atrial sensitivity. RESULTS: The algorithm changed the baseline sensitivity from 0.57 +/- 0.23 mV during the test to 0.39 +/- 0.20 mV after the final rest period (P < 0.05). During the test 12.6 +/- 10.2 adaptations of the sensitivity occurred (range 0-33). In eight patients atrial undersensing occurred in 4.4% +/- 7.5% of the cycles (4-458 unsensed P waves). In these patients, the algorithm continuously adjusted the sensitivity towards more sensitive values, operating 19.1 +/- 18.3 changes compared with 5.4 +/- 7.3 changes in patients without undersensing (P = 0.009). Oversensing did not occur. CONCLUSION: The autosensing algorithm effectively optimized atrial sensitivity in VDD pacing. In patients with atrial undersensing the algorithm continuously remained near the most sensitive settings, thus reacting as intended. A faster sensitivity adjustment of the system would be desirable.

Activities of Daily Living↗

Computerized processing of two-dimensional echocardiograms for the quantification of left ventricular regional contractility.

A new practical method of computer digital image processing of two-dimensional echocardiograms was developed for the quantification of the left ventricular regional contractility. Short axis, cross-sectional images of the left ventricle at the levels of the mitral valve, papillary muscle and apex were recorded by a phased array sector scanner. The echo data recorded on video tape were transfered to a minicomputer through the interface circuits and digitized and processed automatically. Automatic edge detection of the endocardial and epicardial walls was performed by applying sequential steps, including smoothing, dynamic thresholding, region growing and filling small holes. The rationale for edge detection depended upon the assumptions that the abrupt changes of the gray levels occurred at the boundaries and that the points with the maximum gradient values are boundaries of the left ventricular wall. Best-fit contours of endocardial and epicardial edges were drawn by fitting a spline. The short axis cross-sectional left ventricular wall at each level was divided into eight segments, with the center of gravity of enddiastolic left ventricular cavity and the axis connecting this with the posterior end of the right side of the septum being used as the reference point and line. The segmental hemiaxis, area and wall thickness were measured every 33 msec from end-diastole during the cardiac cycle and the systolic percent changes were calculated automatically by a computer. Regional contractility of the left ventricle was evaluated by systolic percent changes of the segmental hemiaxis, area and wall thickness. The measured values in a patient with dilated cardiomyopathy were lower than those of a normal subject, probably reflecting myocardial damage of the left ventricle. Although there are some points to be improved, including a better system for transferring echo data to the computer and the evaluation of the validity of this fixed reference system, it is likely that computer analysis of the short axis cross-sectional echocardiogram of the left ventricle will be useful in a clinical setting.

Cardiomyopathy, Dilated↗

[Longitudinal evaluation of aerobic capacity determined by torque auto-controlled system with the feedback of photoelectric pulse].

We have previously developed a unique and simple procedure for assessing cardiorespiratory fitness. The present investigation was conducted to evaluate whether an aerobic index determined by torque auto-controlled system with the feedback of photoelectric pulse could sufficiently approximate the cardiorespiratory fitness represented by anaerobic threshold (AT) and maximal oxygen uptake (VO2max). Analysis of the cross-sectional data indicated that the aerobic score (AS: K (WR/Wt)/HR; where WR = mean work rate during 12-min cycling, Wt = weight, and HR = mean heart rate during 12-min cycling) determined by the torque auto-controlled system was significantly correlated with directly measured VO2/AT (r = 0.922, 76 males; r = 0.814, 34 females). Cross-validity of the predicted VO2max from the AS was significant and sufficiently high (r = 0.949, 31 males) for use in the general public. In addition, the effects of cycling or jogging training on the AS were longitudinally investigated on 17 females and 1 male. Major effects of the training were significant improvements in the AS, VO2max, and VO2/AT. Delta percentage change [(post-value - pre-value)/pre-value; delta %] in the AS was closely associated (r = 0.718, 8 females) with delta % in VO2/AT. It appears likely from the present investigation that information obtained through the use of our unique system (i.e., the AS) could provide considerably reliable estimate of cardiorespiratory fitness in both males and females.

Adult↗

Response characteristics of pulmocutaneous arterial baroreceptors in the toad, Bufo marinus.

1. Response characteristics of baroreceptors with receptive fields in the pulmocutaneous artery (p.c.a.) were determined in pithed toads by applying pressure steps, ramps, sine waves, and volume infusions into the vascularly isolated and perfused p.c.a. 2. The baroreceptors exhibited phasic and tonic discharge thresholds (30.3 +/- 2.3 and 36.2 +/- 2.8 mmHg respectively) which were above mean arterial pressure values reported for conscious undisturbed toads. They are comparable, in this respect, to non-myelinated mammalian arterial baroreceptors. 3. The maximum-phasic and minimum-adapted discharge frequencies of the p.c.a. baroreceptors were low (30 and 2-3 spikes s-1, respectively), but resembled those reported for mammalian non-myelinated baroreceptors when an adjustment was made for the difference in the temperature of mammalian and amphibian preparations. 4. The sensitivity of the baroreceptor discharge frequency to pressure (delta F/delta P) was estimated from pressure-step and pressure-ramp stimuli. Both estimates were greater than those reported for mammalian systemic arterial baroreceptors after the values were normalized to the maximum discharge frequency of the receptors. delta F/delta P and saturation discharge frequency values estimated from ramp stimuli increased with the dP/dt of pressure ramps. 5. The diameter of the p.c.a. was measured by sonomicrometry in toads anaesthetized with urethane. The diameter pulsation was 7.7 +/- 0.3% of the mean diameter (3.5 +/- 0.1 mm) at a mean pulse pressure of 22 +/- 1 mmHg, and Peterson's pressure-strain modulus was calculated to be 4.0 X 10(5) +/- 0.3 X 10(5) dyn cm-2, which suggests that the p.c.a. is highly compliant, and in this respect is comparable to the pulmonary artery, but not to systemic arteries, in mammals. Baroreceptor discharge began near the point of peak dynamic compliance (dV/dP) and continued as dV/dP decreased. Increasing the rate of infusion reduced the peak dV/dP, but increased the baroreceptor discharge frequency. 6. The response to sinusoidal oscillating pressure stimuli was distorted by rectification. Increasing the frequency of sinusoidal stimulation over the range 0.05-1.0 cycles s-1 reduced the number of spikes per cycle, but increased the mean discharge frequency.

Action Potentials↗

Attenuated respiratory compensation during rapidly incremented ramp exercise.

The fall in end-tidal and arterial P(CO2) may be delayed relative to the lactate threshold (LT) or absent, depending on the slope of the ramp exercise function. Ventilation (VE), gas exchange (V(O2), V(CO2)) and acid-base status were examined during slow (SR, 8 W x min(-1)) and fast (FR, 65 W x min(-1)) ramp cycle exercise in seven males. VE, V(O2), V(CO2), and end-tidal gas tensions (PETO2, PET(CO2)) were determined breath-by-breath. Peak V(O2) (V(O2,peak)) was similar in SR and FR. V(CO2) and VE were similar during submaximal exercise. At V(O2,peak), VE was similar but V(CO2) was lower in SR than FR. With exercise, PET(CO2) increased at work rates below LT. At WRs > or =90%-V(O2,peak), PET(CO2) decreased below 0 W values in SR but not FR. Alveolar P(CO2)2 slope (PA(CO2)) increased with increasing WRs. Above LT, PA(CO2) was lower in SR than FR. Time of expiration (TE) decreased with increasing WRs, but no difference between SR and FR was observed. The higher PET(CO2) in FR at higher WRs was attributed in part, to a higher PA(CO2) as no differences were observed in TE.

Acid-Base Equilibrium↗

Regulation of actomyosin ATPase by a single calcium-binding site on troponin C from crayfish.

Equilibrium-binding studies at 4 degrees C show that, in the instance of crayfish, troponin C contains only one Ca-binding site with an affinity in the range of physiological free [CA2+] (K = 2 X 10(5) M-1). At physiological levels of Mg2+, this site does not bind Mg2+. In the complexes of troponin C-troponin I, troponin and troponin-tropomyosin, the regulatory Ca-specific site exhibits a 10- to 20-fold higher affinity (K = 2-4 X 10(6) M-1). The latter affinity is reduced to that of troponin C upon incorporation of the troponin-tropomyosin complex into the actin filament (regulated actin), as determined at 4 degrees C by the double isotope technique. The Ca-binding constant is again shifted to a higher value (7 X 10(6) M-1) when regulated actin is associated with nucleotide-free myosin. Both crayfish myofibrils and rabbit actomyosin regulated by crayfish troponin-tropomyosin display a steep rise in ATPase activity with [Ca2+]. Comparison of the pCa/ATPase relationship and the Ca-binding properties at 25 degrees C for the crayfish troponin-regulated actomyosin indicates that while the threshold [Ca2+] for activation corresponds to the range of [Ca2+] where the regulatory site in its low affinity state (K = 1 X 10(5) M-1) starts to bind Ca2+ significantly, full activation is reached at [Ca2+] for which the Ca-specific site in its high affinity state (K = 3 X 10(6) M-1) approaches saturation. These results suggest that, in the actomyosin ATPase cycle, there are at least two calcium-activated states of regulated actin (one low and one high), the high affinity state being induced by interactions of myosin with actin in the cycle.

Actins↗

Heterogeneity of metabolic parameters in the left ventricular myocardium and its relation to local blood flow.

It is well established that myocardial blood flow is heterogeneous on the local level. During recent years comprehensive studies have been undertaken to assess the relation between myocardial metabolism and spatial blood flow heterogeneity. Based on the type of measurements two major groups of studies have been performed: enzyme activity and tissue metabolite level assessments. Enzyme activity measurements have provided only limited insight into the coupling of local metabolism and flow. This is probably due to the fact that, in addition to estimated Vmax values, local substrate affinity (Km values) and substrate concentrations affect the metabolite fluxes. However, the latter two variables remain normally unknown. In contrast, valuable insight has been obtained concerning flow-metabolism matching from tissue metabolite measurements, especially when connected with mathematical model analyses. The latter permitted the calculation of metabolic flux rates (e.g., production of oxidation water, citric acid cycle flux, glucose uptake, fatty acid uptake) or the translation of the metabolic indexes into physiologically meaningful local metabolite concentrations (e.g., free cytosolic adenosine). The bottom line of the studies reported to date is that the broad range of myocardial flows observed under resting control conditions correlates with local metabolism possibly affected by spatial differences in adrenergic stimulation. Thus, high flow samples exhibit a higher oxidative metabolism than low flow samples. As a result the flow threshold below which local myocardial ischemia ensues is higher in control high flow samples. The importance of these findings with respect to local flow-metabolism matching is underlined by the finding that the probability of developing an infarction following ischemia/reperfusion is related to the functional state of the myocardium under control conditions, i.e., the local level of flow-metabolism matching.

Animals↗