Recovery Half-time Research Articles

Astrocytic regulation of the recovery of extracellular potassium after seizures in vivo.

Glial cells are believed to play a major role in the regulation of the extracellular potassium concentration ([K+]o), particularly when the [K+]o is increased. Using ion-selective electrodes, we compared the [K+]o changes in the dentate gyrus of urethane-anaesthetized adult rats in the presence of reactive astrocytes and after reduction of glial function. The regulation of [K+]o in the dentate gyrus was determined by measuring the ceiling level of [K+]o and the half-time of recovery of [K+]o during and after seizures produced by 20 Hz trains of stimulation to the angular bundle. Reactive astrocytes were induced by repeated seizures and their presence was confirmed by a qualitative increase in glial fibrillary acidic protein (GFAP) and vimentin immunoreactivity. To inhibit glial function, fluorocitrate (FC), a reversible metabolic inhibitor, or alpha-aminoadipate (alpha-AA), an irreversible toxin, was injected into the dentate gyrus region, and the regulation of [K+]o was monitored for 8 h or 2 days later, respectively. After alpha-aminoadipate, loss of astrocytes in the dentate gyrus was demonstrated by loss of staining for GFAP. In the presence of reactive astrocytes there was no significant change in the peak [K+]o during seizures or the half-time of recovery of [K+]o after seizures compared to control animals. alpha-Aminoadipate significantly slowed the rate of recovery of [K+]o, but did not change the ceiling [K+]o. Fluorocitrate reversibly decreased the ceiling [K+]o, but also slowed the rate of recovery of [K+]o. Overall our results suggest that normal glial function is required for the recovery of elevated [K+]o after seizures in vivo.

Pulsed-Dose-Rate and Low-Dose-Rate Brachytherapy: Comparison of Sparing Effects in Cells of a Radiosensitive and a Radioresistant Cell Line

Pulsed-dose-rate regimens are an attractive alternative to continuous low-dose-rate brachytherapy. However, apart from data obtained from modeling, only a few in vitro results are available for comparing the biological effectiveness of both modalities. Cells of two human cell lines with survival fractions of 80% (RT112) and 10% (HX142) after a single dose of 2 Gy and with different halftimes for split-dose recovery and low-dose recovery were used. The cells were irradiated with a continuous low dose rate (80 cGy per hour) or with pulsed dose rate. Two different pulsed dose rates were tested: 4.25 Gy/h and 63 Gy/h. The effects of dose per pulse and the length of the interval between the pulses were investigated while keeping the overall treatment time constant. Survival after low-dose-rate irradiation was indistinguishable from that after pulses of 4.25 Gy/h in cells of both cell lines. Survival decreased with increasing dose per pulse. When the dose rate during the pulses was increased, survival decreased even further. This effect was most pronounced for the radiosensitive HX142 cells. In clinical pulsed-dose-rate brachytherapy, iridium sources move stepwise through the implant and deliver pulses at a high dose rate locally. These high-dose-rate pulses produce greater biological effectiveness compared to continuous low dose rate; this should be taken into account.

Release of Ca2+ from the sarcoplasmic reticulum increases mitochondrial [Ca2+] in rat pulmonary artery smooth muscle cells.

1. The Ca2+-sensitive fluorescent indicator rhod-2 was used to measure mitochondrial [Ca2+] ([Ca2+]m) in single smooth muscle cells from the rat pulmonary artery, while simultaneously monitoring cytosolic [Ca2+] ([Ca2+]i) with fura-2. 2. Application of caffeine produced an increase in [Ca2+]i and also increased [Ca2+]m. The increase in [Ca2+]m occurred after the increase in [Ca2+]i, and remained elevated for a considerable time after [Ca2+]i had returned to resting values. 3. The protonophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), which causes the mitochondrial membrane potential to collapse, markedly attenuated the increase in [Ca2+]m following caffeine application and also increased the half-time for recovery of [Ca2+]i to resting values. 4. Activation of purinoceptors with ATP also produced increases in both [Ca2+]i and [Ca2+]m in these smooth muscle cells. In some cells, oscillations in [Ca2+]i were observed during ATP application, which produced corresponding oscillations in [Ca2+]m and membrane currents. 5. This study provides direct evidence that Ca2+ release from the sarcoplasmic reticulum, either through ryanodine or inositol 1,4, 5-trisphosphate (InsP3) receptors, increases both cytosolic and mitochondrial [Ca2+] in smooth muscle cells. These results have potential implications both for the role of mitochondria in Ca2+ regulation in smooth muscle, and for understanding how cellular metabolism is regulated.

Cerebral metabolic abnormalities in congestive heart failure detected by proton magnetic resonance spectroscopy

OBJECTIVESUsing proton magnetic resonance spectroscopy, we investigated cerebral metabolism and its determinants in congestive heart failure (CHF), and the effects of cardiac transplantation on these measurements.BACKGROUNDFew data are available about cerebral metabolism in CHF.METHODSFifty patients with CHF (ejection fraction ≤35%) and 20 healthy volunteers were included for this study. Of the patients, 10 patients underwent heart transplantation. All subjects performed symptom-limited bicycle exercise test. Proton magnetic resonance spectroscopy (1H MRS) was obtained from localized regions (8 to 10 ml) of occipital gray matter (OGM) and parietal white matter (PWM). Absolute levels of the metabolites (N-acetylaspartate, creatine, choline, myo-inositol) were calculated.RESULTSIn PWM only creatine level was significantly lower in CHF than in control subjects, but in OGM all four metabolite levels were decreased in CHF. The creatine level was independently correlated with half-recovery time and duration of heart failure symptoms in PWM (r = −0.56, p < 0.05), and with peak oxygen consumption and serum sodium concentration in OGM (r = 0.58, p < 0.05). Cerebral metabolic abnormalities were improved after successful cardiac transplantation.CONCLUSIONSThis study shows that cerebral metabolism is abnormally deranged in advanced CHF and it may serve as a potential marker of the disease severity.

Peripheral muscle ergoreceptors and ventilatory response during exercise recovery in heart failure.

Recent studies have suggested that the increased ventilatory response during exercise in patients with chronic heart failure was related to the activation of muscle metaboreceptors. To address this issue, 23 patients with heart failure and 7 normal subjects performed arm and leg bicycle exercises with and without cuff inflation around the arms or the thighs during recovery. Obstruction slightly reduced ventilation and gas exchange variables at recovery but did not change the kinetics of recovery of these parameters compared with nonobstructed recovery: half-time of ventilation recovery was 175 +/- 54 to 176 +/- 40 s in patients and 155 +/- 66 to 127 +/- 13 s in controls (P < 0.05, patients vs. controls, not significant within each group from baseline to obstructed recovery). We conclude that muscle metaboreceptor activation does not seem to play a role in the exertion hyperventilation of patients with heart failure.

Productivity of intensified crop-fallow rotations in the Trenbath model

Management of crop—fallow rotations should strike a balance between exploitation, during cropping, and restoration of soil fertility during the fallow period. The ‘Trenbath’ model describes build-up of soil fertility during a fallow period by two parameters (a maximum level and a half-recovery time) and decline during cropping as a simple proportion. The model can be used to predict potential crop production for a large number of management options consisting of length of cropping period and duration of fallow. In solving the equations, the model can be restricted to ‘sustainable’ systems, where fallow length is sufficient to restore soil fertility to its value at the start of the previous cropping period. The model outcome suggests that the highest yields per unit of land can be obtained by starting a new cropping period after soil fertility has recovered to 50–60% of its maximum value. This prediction is virtually independent of the growth rate of the fallow vegetation. The nature of the fallow vegetation (natural regrowth, planted trees, or cover crops) mainly influences the crop yield by modifying the required duration of fallow periods. Intensification of land use by shortening fallow periods will initially increase returns per unit land at the likely costs of returns per unit labor. When fallows no longer restore soil fertility to 50% of the maximum, overall productivity will decline both per unit land and per unit labor, unless external inputs replace the soil fertility restoring functions of a fallow.

Performance of active Photosystem II centers in photoinhibited pea leaves

Effects of photoinhibition on photosynthesis in pea (Pisum sativum L.) leaves were investigated by studying the relationship between the severity of a photoinhibitory treatment (measured as Fv/Fm) and several photoacoustic and chlorophyll a fluorescence parameters. Because of the observed linear relationship between the decline of Fv/Fm and the potential oxygen evolution rate determined by the photoacoustic method, the parameter Fv/Fm was used as an indicator for the severity of photoinhibition. Our analysis revealed that part of the Photosystem II (PS II) reaction centers is inactive in oxygen evolution and is also less sensitive to photoinhibition. Correcting the parameter qP (fraction of open PS II reaction centers) for inactive PS II centers unveiled a strong increase of qP in severely inhibited pea leaves, indicating that the inactivated active centers do no longer contribute to qP and that photoinhibition has an all or none effect on PS II centers. Analysis of qE (energy quenching) demonstrated its initial increase possibly associated with dephosphorylation of LHC II. Analysis of qI (photoinhibition dependent quenching) showed that the half-time of recovery of qI increases steeply below an Fv/Fm of 0.65. This increase of the relaxation half-time corresponds with a decrease of the electron transport rate J and tentatively indicates that the supply of ATP, needed for the recovery, starts to decrease. The data indicate the necessity of correcting for inactive centers in order to make valuable conclusions about effects of photoinhibition on photosynthetic parameters.

Sediment Transport and Hg Recovery in Lavaca Bay, as Evaluated from Radionuclide and Hg Distributions

Mercury was released in the late 1960s from a chlor-alkali facility managed by ALCOA and deposited into sediments of Lavaca Bay, TX. Sediments have recorded this event as a well-defined subsurface concentration maximum. Radionuclide, mercury, X-radiography, and grain size data from sediment cores taken in 1997 at 15 stations in Lavaca Bay were used to assess sediment and Hg movements in the bay. Sediment accumulation rates were calculated from bomb fallout nuclide (137Cs, 239,240Pu) peaks in 1963 and from the steady-state delivery of 210Pb from the atmosphere. Sedimentation rates are highest (∼2 cm/yr) at near-shore sites near the ALCOA facility and generally decrease away from shore. Sedimentation rates in some areas are likely influenced by anthropogenic activities such as dredging. Particle reworking, as assessed from 7Be measurements, is generally restricted to the upper 2−7 cm of sediments. Numerical simulations of Hg profiles using measured sedimentation and mixing parameters indicate that at most sites high remnant mercury concentrations at 15−60 cm depth cannot supply substantial amounts of Hg to surface sediments. Assuming no future Hg supplies, Hg concentrations in surface sediments are predicted to decrease exponentially with a recovery half-time of 4 ± 2 years.

PET studies of peripheral catechol-O-methyltransferase in non-human primates using [18F]Ro41-0960.

We previously reported the results of PET (positron emission tomography) studies of [18F]Ro41-0960, a potent COMT inhibitor, in baboon brain. Here we report an evaluation of the pharmacokinetics and specificity of binding of [18F]Ro41-0960 in the peripheral organs of baboon. We observed a rapid clearance of the tracer from the heart and no significant uptake in the lung. In contrast, there was a high uptake and slow clearance in both kidney and liver, consistent with a high level of COMT in these peripheral organs. We also observed a dose-dependent inhibition of [18F]Ro41-0960 uptake by unlabeled Ro41-0960 (ED50 was 0.5 mg/kg in liver, and <0.01 mg/kg in kidney), with a halftime for recovery of COMT of about 25 h at the dose of 2 mg/kg of unlabeled Ro41-0960. This indicates a reversible tight binding interaction between COMT and Ro41-0960 in both liver and kidney and suggests that [18F]Ro41-0960 may be a useful radiotracer for future examination of the functional activity of COMT in the human body.

Effects of NaHCO3 loading on acid-base balance, lactate concentration, and performance in racing greyhounds.

This investigation examined the effects of NaHCO3 loading on lactate concentration ([La]), acid-base balance, and performance for a 603. 5-m sprint task. Ten greyhounds completed a NaHCO3 (300 mg/kg body weight) and control trial in a crossover design. Results are expressed as means +/- SE. Presprint differences (P < 0.05) were found for NaHCO3 vs. control, respectively, for blood pH (7.47 +/- 0.01 vs. 7.42 +/- 0.01), HCO-3 (28.4 +/- 0.4 vs. 23.5 +/- 0.3 meq/l), and base excess (5.0 +/- 0.3 vs. 0.2 +/- 0.3 meq/l). Peak blood [La] increased (P < 0.05) in NaHCO3 vs. control (20.4 +/- 1.6 vs. 16.9 +/- 1.3 mM, respectively). Relative to control, NaHCO3 produced a greater (P < 0.05) reduction in blood base excess (-18.5 +/- 1.4 vs. -14.1 +/- 0.8 meq/l) and HCO-3 (-17.4 +/- 1.2 vs. -12.8 +/- 0.7 meq/l) from presprint to postexercise. Postexercise peak muscle H+ concentration ([H+]) was higher (P < 0.05) in NaHCO3 vs. control (158.8 +/- 8.8 vs. 137.0 +/- 5.3 nM, respectively). Muscle [H+] recovery half-time (7.2 +/- 1.6 vs. 11.3 +/- 1.6 min) and time to predose values (22.2 +/- 2.4 vs. 32.9 +/- 4.0 min) were reduced (P < 0.05) in NaHCO3 vs. control, respectively. No differences were found in blood [H+] or blood [La] recovery curves or performance times. NaHCO3 increased postexercise blood [La] but did not reduce the muscle or blood acid-base disturbance associated with a 603.5-m sprint or significantly affect performance.

Electrophysiological evidence for putative subtypes of neurotensin receptors in guinea-pig mesencephalic dopaminergic neurons

Electrophysiologically identified mesencephalic dopaminergic neurons were examined by means of extra- and intracellular microelectrodes in coronal slices of guinea-pig brain. Neurotensin and its C-terminal fragment (8–13) were equipotent in the enhancement of spontaneous neuronal firing rate ( ec 50 values 81.9 and 72.6 nM, respectively). The duration of response was significantly longer and more variable for neurotensin compared to neurotensin fragment (8–13) (mean half-time of recovery 423±44 and 100±14 s, respectively, for peptides applied at 300 nM). The initial fast phase of excitatory responses to neurotensin receptor agonists was associated with membrane depolarization (when assessed in current-clamp mode) or with inward currents (when assessed in voltage-clamp mode), whereas prolonged excitation was associated with a slowly occurring and long-lasting change in the late afterhyperpolarization. Two kinetically distinct components were revealed in responses to neurotensin and neurotensin fragment (8–13) by the use of SR48692 and SR142948, two selective non-peptide neurotensin receptor antagonists. SR142948 (100 nM) potently antagonized responses to both agonists [response was reduced by 66±5% and 74±9% for neurotensin and neurotensin fragment (8–13), respectively] and caused a rightward shift in the concentration–response curve for neurotensin. On the other hand, SR48692 (100 nM) selectively inhibited the slow (late afterhyperpolarization-dependent) component, without altering the response amplitude; the half-time of recovery was reduced by 71±6% and 65±5% of control values for responses induced by neurotensin (300 nM) and neurotensin fragment (8–13) (300 nM), respectively. In addition, neurotensin, but not neurotensin fragment (8–13), provoked SR48692-sensitive and long-lasting attenuation of dopamine-induced inhibitory responses. It is suggested that two subtypes of neurotensin receptors are present in dopaminergic neurons, based on the differences in agonist and antagonist sensitivity, kinetic properties and the membrane mechanisms involved.

Rapid diffusion of green fluorescent protein in the mitochondrial matrix.

It is thought that the high protein density in the mitochondrial matrix results in severely restricted solute diffusion and metabolite channeling from one enzyme to another without free aqueous-phase diffusion. To test this hypothesis, we measured the diffusion of green fluorescent protein (GFP) expressed in the mitochondrial matrix of fibroblast, liver, skeletal muscle, and epithelial cell lines. Spot photobleaching of GFP with a 100x objective (0.8-micron spot diam) gave half-times for fluorescence recovery of 15-19 ms with >90% of the GFP mobile. As predicted for aqueous-phase diffusion in a confined compartment, fluorescence recovery was slowed or abolished by increased laser spot size or bleach time, and by paraformaldehyde fixation. Quantitative analysis of bleach data using a mathematical model of matrix diffusion gave GFP diffusion coefficients of 2-3 x 10(-7) cm2/s, only three to fourfold less than that for GFP diffusion in water. In contrast, little recovery was found for bleaching of GFP in fusion with subunits of the fatty acid beta-oxidation multienzyme complex that are normally present in the matrix. Measurement of the rotation of unconjugated GFP by time-resolved anisotropy gave a rotational correlation time of 23.3 +/- 1 ns, similar to that of 20 ns for GFP rotation in water. A rapid rotational correlation time of 325 ps was also found for a small fluorescent probe (BCECF, approximately 0.5 kD) in the matrix of isolated liver mitochondria. The rapid and unrestricted diffusion of solutes in the mitochondrial matrix suggests that metabolite channeling may not be required to overcome diffusive barriers. We propose that the clustering of matrix enzymes in membrane-associated complexes might serve to establish a relatively uncrowded aqueous space in which solutes can freely diffuse.

Kinetics of recovery of the dark-adapted salamander rod photoresponse.

The kinetics of the dark-adapted salamander rod photocurrent response to flashes producing from 10 to 10(5) photoisomerizations (Phi) were investigated in normal Ringer's solution, and in a choline solution that clamps calcium near its resting level. For saturating intensities ranging from approximately 10(2) to 10(4) Phi, the recovery phases of the responses in choline were nearly invariant in form. Responses in Ringer's were similarly invariant for saturating intensities from approximately 10(3) to 10(4) Phi. In both solutions, recoveries to flashes in these intensity ranges translated on the time axis a constant amount (tauc) per e-fold increment in flash intensity, and exhibited exponentially decaying "tail phases" with time constant tauc. The difference in recovery half-times for responses in choline and Ringer's to the same saturating flash was 5-7 s. Above approximately 10(4) Phi, recoveries in both solutions were systematically slower, and translation invariance broke down. Theoretical analysis of the translation-invariant responses established that tauc must represent the time constant of inactivation of the disc-associated cascade intermediate (R*, G*, or PDE*) having the longest lifetime, and that the cGMP hydrolysis and cGMP-channel activation reactions are such as to conserve this time constant. Theoretical analysis also demonstrated that the 5-7-s shift in recovery half-times between responses in Ringer's and in choline is largely (4-6 s) accounted for by the calcium-dependent activation of guanylyl cyclase, with the residual (1-2 s) likely caused by an effect of calcium on an intermediate with a nondominant time constant. Analytical expressions for the dim-flash response in calcium clamp and Ringer's are derived, and it is shown that the difference in the responses under the two conditions can be accounted for quantitatively by cyclase activation. Application of these expressions yields an estimate of the calcium buffering capacity of the rod at rest of approximately 20, much lower than previous estimates.

Exercise Capacity and Kinetics of Recovery Oxygen Consumption after Exercise in Patients with Mitral Stenosis: Effects of Percutaneous Balloon Mitral Valvuloplasty and Exercise Training

Background:The kinetics of recovery oxygen consumption plays an important role in determining exercise capacity. This study was performed to evaluate the kinetics of recovery oxygen consumption and the effects of percutaneous balloon mitral valvuloplasty (PMV and exercise training on the recovery kinetics in mitral stenosis (MS. Method:Thirty patients with MS (valve area 1.0 cm 2 and thirty age-and size-matched healthy volunteers were included for this study. All subjects performed symptom-limited, upright, graded bicycle exercise. Patients were randomized to either the exercise training group or the non-training group after successful PMV (valve area 1.5 cm2 and mitral regurgitation grade 2. The exercise group performed daily exercise training for 3 months. Results:Half-recovery time of peak oxygen consumption (T1/2VO2 was significantly delayed in MS patients than in the volunteers (12,042 sec vs 595, p<0.01). Peak oxygen consumption (pVO2, ml/min/kg) was significantly increased in both the training (16.8±4.9 to 25.3±6.9 and the non-training group (16.3±5.1 to 19.6±6.0 3 months after PMV. T1/2VO2 was significantly shortened in the training group (12,439 to 7,613, p<0.01, but not in the non-training group (11,446 to 10,944 sec, p= 0.12 at 3 months follow-up. The degrees of symptomatic improvement after PMV were more closely correlated with the changes of T1/2VO2 than those of pVO2. Conclusion:Kinetics of recovery oxygen consumption was markedly delayed in MS patients, but the kinetics improved after exercise training but not after PMV alone. These results suggest that adjunctive exercise training may be useful for improvement of recovery kinetics and subjective symptoms after PMV. (Korean Circulation J 1998;28(4 :545-552

Physiological inactivation of vasoactive hormones in rainbow trout

Hormone titers are affected by interplay between secretion and inactivation processes. While secretion is a focal process, inactivation mechanisms are often complex and poorly understood. In the present study, inactivation of cardiovascular regulatory hormones was examined from a physiological perspective by analyzing the half-time (t½) for recovery of dorsal and ventral aortic and central venous pressure, cardiac output, heart rate, and systemic and branchial vascular resistance following infusion or injection of hormones into conscious rainbow trout, Oncorhynchus mykiss. When possible, these were compared to recovery t½ of isolated vessel rings in vitro. The t½ for epinephrine or norepinephrine recovery in vivo was 3–4 min, approximately twice as long as recovery t½ for isolated celiacomesenteric and epibranchial artery rings in vitro. Thus, the rate-limiting step in vascular relaxation is the concentration of circulating catecholamine concentrations, and not metabolic or mechanical events within the vascular wall. The in vivo recovery t½ following angiotensin II (ANG II) infusion was 6–7 min, nearly twice that of catecholamines, but also greater than the t½ following bolus ANG II injection, inhibition of angiotensin converting enzyme with captopril or injection of trout bradykinin. Arginine vasotocin (AVT) recovery t½ in vivo, was considerably longer (20–30 min) than either catecholamine or ANG II t½ and longer than AVT recovery t½ of isolated vessels in vitro (5–6 min). The inactivation kinetics of catecholamines are consistent with circulatory convection-limited processes and do not appear to be limited by either tissue uptake or enzymatic degradation. This is probably the fastest type of ‘on-off’ endocrine regulation in fish. Inactivation of ANG II and bradykinin are also convection limited, but ANG II metabolism may become saturated with high doses of exogenous ANG II. AVT inactivation is not convection limited and may compensate for a quantitatively lower capacity of the pituitary for peptide secretion, or less emphasis on AVT as an on/off effector of vascular resistance. J. Exp. Zool. 279:254–264, 1997. © 1997 Wiley-Liss, Inc.

Delayed recovery of nerve conduction and vibratory sensibility after ischaemic block in patients with diabetes mellitus

OBJECTIVESTo determine if the recovery of nerve function after ischaemic block is impaired in patients with diabetes mellitus relative to healthy controls.METHODSMedian nerve impulse conduction and vibratory thresholds in the...

Comparison of responses to rat and human adrenomedullin in the hindlimb vascular bed of the cat

Responses to rat (r) adrenomedullin (ADM) and human (h) ADM were compared in the hindlimb vascular bed of the cat under conditions of controlled blood flow. Intra-arterial injections of rADM and hADM in doses of 0.03–1 nmol caused dose-related decreases in hindlimb perfusion pressure. In terms of relative vasodilator activity, rADM was similar to hADM. The time course of the vasodilator response and the recovery half times ( T 1/2) for the vasodilator response to rADM and hADM were not significantly different. Decreases in hindlimb perfusion pressure in response to rADM and hADM were not altered by the calcitonin gene-related peptide receptor antagonist, rCGRP(8–37), at the same time, vasodilator responses to calcitonin gene-related peptide (CGRP) were significantly reduced. The T 1/2 of the vasodilator response to rADM and hADM were significantly greater after administration of the cAMP-selective, type IV phosphodiesterase inhibitor, rolipram. These data demonstrate that decreases in hindlimb perfusion pressure in response to rADM and hADM are similar and that vasodilator responses to rADM are not dependent on the activation of CGRP receptors in the hindlimb vascular bed of the cat. These data further suggest that decreases in hindlimb perfusion pressure in response to rADM are mediated by smooth muscle increases in cAMP levels.

Influence of cytosolic pH on in vivo assessment of human muscle mitochondrial respiration by phosphorus magnetic resonance spectroscopy.

The authors present an in vivo phosphorus magnetic resonance spectroscopy systematic study on the effects of cytosolic pH on skeletal muscle mitochondrial respiration in human calf muscle. In 49 normal subjects, the effect of cytosolic pH on kinetics of phosphocreatine and adenosine diphosphate recovery and on maximum rate of mitochondrial adenosine triphosphate production (Q(MAX)) was evaluated. The results show a strong relationship between the rate of postexercise phosphocreatine recovery and the lowest value of cytosolic pH reached during recovery from exercise (termed minimum pH; r = 0.89); in contrast, both adenosine diphosphate recovery halftime and Q(MAX) were independent of cytosolic pH at the end of exercise.

GREATER PERIPHERAL THAN CENTRAL ADAPTATION TO AEROBIC TRAINING IN MITOCHONDRIAL MYOPATHIES 186

In theory, limited aerobic capacity in patients with mitochondrial myopathies (MM) could be secondary to the primary disease process or effects of chronic deconditioning. The objectives of this study were to determine 1) whether patients with MM could respond to aerobic training and 2) their ability to adapt centrally versus peripherally relative to patients with other chronic non-metabolic myopathies (NM). 10 patients with MM, 6 patients with NM, and 5 sedentary healthy control subjects were evaluated before and after undergoing a similar aerobic training regimen for 8 weeks. Aerobic capacity(METs) was estimated from performance on a graded exercise test to 85% HRmax. Heart rate for an identical submaximal exercise workload was used as an index of central adaptation. Blood lactate at rest and after a constant submaximal workload, and muscle oxidative ATP resynthesis after ischemic exercise (as reflected by the ADP recovery half time [T1/2] estimated by phosphorus magnetic resonance spectroscopy) were used as indices of peripheral muscle oxidative capacity. The mean initial fitness level was similar in MM and NM, and significantly lower than that of healthy controls(p<.01). Training resulted in a significant improvement in aerobic capacity in all groups, but MM improved 20% more than NM and 27% more than controls. Decreases in HR were detected in both patient groups (p<.01) but only MM showed significant improvement (p<.01) in blood lactate concentrations(50%) and ADP T1/2 (over 2-fold) after training. Thus, both MM and NM benefit from aerobic training, but MM benefit even more than NM. The difference appears to be due to greater peripheral adaptation in MM and supports the hypothesis that partially reversible limitation at the muscle level dominates the training response in patients with mitochondrial myopathy.

Simultaneous measurements of lactate and blood flow during hypoxia and recovery from hypoxia in a localized region in the brain of the anesthetized rabbit

We observed simultaneous changes in lactate level and regional blood flow (rBF) in the brain of the anesthetized rabbit by using localized proton magnetic resonance spectroscopy ( 1H MRS) and laser Doppler flowmetry. The volume of interest of 0.5 ml for 1H MRS contained mostly thalamic nuclei. During hypoxia peak area for lactate increased up to 57% of that from N-Acetylaspartate. While the rBF increased during hypoxia up to 260% of the control, oxygen delivery (rBF×arterial oxygen content) decreased. In the normoxic recovery period following hypoxia, the rBF recovered slowly and a consequent overshoot of oxygen delivery was observed. The multiple and stepwise linear regression analyses revealed that the averaged decrease in oxygen delivery during hypoxia was the most significant independent variable for the increase in lactate during hypoxia (correlation coefficient; r 2=0.68) and also that the increase in lactate during hypoxia was the most significant independent variable for the time for half-recovery of rBF ( r 2=0.75). These results suggest that the increase in lactate during hypoxia is due to the deficiency of oxygen delivery and that the increase in lactate during hypoxia prolongs the period of enhancement of rBF during recovery from hypoxia.