31P nuclear magnetic resonance spectroscopy study of the anaerobic threshold in humans

The relationships among the lactate threshold (LT), ventilatory threshold (VT), and intracellular biochemical events in exercising muscle have not been well defined. Therefore 14 normal subjects performed incremental plantar flexion to exhaustion on 2 study days, the first for determination of LT and VT and the second for continuous 31P nuclear magnetic resonance spectroscopy of calf muscle. Exercising calf muscle pH fell precipitously at 66.4 +/- 3.4% (SE) of the maximum O2 uptake (VO2max) and was termed the intramuscular pH threshold. This did not occur at a significantly different metabolic rate from that at the LT (78.6 +/- 5.9% VO2max) or at the VT (75.0 +/- 4.1% VO2max, P = 0.15 by analysis of variance). Four subjects showed an intramuscular pH threshold and VT without a perceptible rise in forearm venous blood lactate. It is concluded that traditional markers of the "anaerobic threshold," the LT and VT, occur as intramuscular pH becomes acid for a group of normal subjects undergoing incremental exercise to exhaustion. It is speculated that neuronal pathways linking intramuscular biochemical events to the ventilatory control center may explain the intact VT in those subjects without an "intermediary" LT.     

Skeletal muscle ECF pH error signal for exercise ventilatory control

Evans, Allison B., Larry W. Tsai, David A. Oelberg, HomayounKazemi, and David M. Systrom. Skeletal muscle ECF pH error signalfor exercise ventilatory control. J. Appl.Physiol. 84(1): 90-96, 1998.An autonomic reflexlinking exercising skeletal muscle metabolism to central ventilatorycontrol is thought to be mediated by neural afferents having freeendings that terminate in the interstitial fluid of muscle. Todetermine whether changes in muscle extracellular fluid pH(pH_e) can provide an errorsignal for exercise ventilatory control,pH_e was measured duringelectrically induced contraction by³¹P-magnetic resonancespectroscopy and the chemical shift of a phosphorylated, pH-sensitivemarker that distributes to the extracellular fluid (phenylphosphonicacid). Seven lightly anesthetized rats underwentunilateral continuous 5-Hz sciatic nerve stimulation in an 8.45-Tnuclear magnetic resonance magnet, which resulted in a mixed lacticacidosis and respiratory alkalosis, with no net change in arterial pH.Skeletal muscle intracellular pH fell from 7.30 ± 0.03 units atrest to 6.72 ± 0.05 units at 2.4 min of stimulation and then roseto 7.05 ± 0.01 units (P < 0.05), despite ongoing stimulation and muscle contraction.Despite arterial hypocapnia, pH_eshowed an immediate drop from its resting baseline of 7.40 ± 0.01 to 7.16 ± 0.04 units (P < 0.05)and remained acidic throughout the stimulation protocol. During the on-and off-transients for 5-Hz stimulation, changes in the pH gradientbetween intracellular and extracellular compartments suggestedtime-dependent recruitment of sarcolemmal ion-transport mechanisms.pH_e of exercising skeletal musclemeets temporal and qualitative criteria necessary for a ventilatorymetaboreflex mediator in a setting where arterial pH doesnot.

     

Systemic oxygen extraction during incremental exercise in patients with severe chronic obstructive pulmonary disease

To determine if decreased systemic oxygen (O₂) extraction contributes to the exercise limit in severe chronic obstructive pulmonary disease (COPD), 40 consecutive incremental cycle ergometer exercise tests performed by such patients, from which a “log-log” lactate threshold (LT) was identified, were compared to those of 8 patients with left ventricular failure (LVF) and 10 normal controls. Pulmonary gas exchange and minute ventilation were measured continuously and arterial blood gas tensions, pH, and lactate concentrations were sampled each minute. Cardiac output (Q˙ _c) was measured by first-pass radionuclide ventriculography. The systemic O₂ extraction ratio (O₂ER) was calculated as arterial − mixed venous O₂ content difference (C _aO₂ − C _vO₂)/C _aO₂. Peak exercise O₂ uptake (V˙O_2peak) was markedly reduced in both COPD and LVF [41 (3) and 42 (3)% predicted, respectively], compared to controls [89 (2)% predicted, P < 0.0001 for each]. Similarly, the LT occurred at a low percentage of predicted maximal oxygen consumption in both COPD and LVF [25 (2) and 27 (3)%] compared to normals [46 (3)%, P < 0.0001 for each]. The systemic O₂ER at peak exercise was severely reduced in COPD [0.36 (0.02)] compared to the other groups [P < 0.0001 for each], for whom it was nearly identical [0.58 (0.03) vs 0.63 (0.04), LVF vs control, P > 0.05]. In the COPD group, an early LT correlated with reduced systemic O₂ER at peak exercise (r = 0.64, P < 0.0001), but not with any index of systemic O₂ delivery. These data suggest that lactic acidemia during exercise in patients with severe COPD is better related to abnormal systemic O₂ extraction than to its delivery and contributes to the exercise limit. Accepted: 10 March 1998     

Central respiratory effects of glutamine synthesis inhibition in dogs

Glutamic acid is an excitatory neurotransmitter that may have a significant role in the central chemical drive of ventilation. Therefore cardiorespiratory function was measured in pentobarbital sodium-anesthetized dogs before and after central inhibition of glutamate metabolism by means of methionine sulfoximine (MSO), a specific inhibitor of glutamine synthase (GS) catalyzing amidation of glutamate to glutamine. GS was inhibited centrally by perfusing the ventriculocisternal space with artificial cerebrospinal fluid (CSF) containing 92.5 mmol MSO per liter at a fixed pH, perfusion rate, and pressure. After GS inhibition, CSF transfer rate of [13N]glutamine synthesized from 13NH4+ amidation of glutamate was reduced five-fold, and minute ventilation increased from 2.90 +/- 0.41 (SE) l/min (0.164 +/- 0.020 l.min-1.kg body wt-1) to 4.46 +/- 0.52 l/min (0.254 +/- 0.029 l.min-1.kg body wt-1). This increase in ventilation with endogenous glutamate and the increase in ventilation previously observed during ventriculocisternal perfusion of exogenous glutamate are compared quantitatively via a model of central neurotransmitter glutamate chemoreception. The results support the hypothesis that the endogenous brain glutamate is important in the central chemical drive of ventilation.     

Skeletal muscle chemoreflex and pHi in exercise ventilatory control

Oelberg, David A., Allison B. Evans, Mirko I. Hrovat, PaulP. Pappagianopoulos, Samuel Patz, and David M. Systrom. Skeletal muscle chemoreflex and pH_i inexercise ventilatory control. J. Appl.Physiol. 84(2): 676-682, 1998.To determinewhether skeletal muscle hydrogen ion mediates ventilatory drive inhumans during exercise, 12 healthy subjects performed three bouts ofisotonic submaximal quadriceps exercise on each of 2 days in a 1.5-Tmagnet for ³¹P-magnetic resonancespectroscopy(³¹P-MRS). Bilaterallower extremity positive pressure cuffs were inflated to 45 Torr duringexercise (BLPP_ex) or recovery(BLPP_rec) in a randomized orderto accentuate a muscle chemoreflex. Simultaneous measurements were madeof breath-by-breath expired gases and minute ventilation, arterializedvenous blood, and by ³¹P-MRS ofthe vastus medialis, acquired from the average of 12 radio-frequencypulses at a repetition time of 2.5 s. WithBLPP_ex, end-exercise minuteventilation was higher (53.3 ± 3.8 vs. 37.3 ± 2.2 l/min;P < 0.0001), arterializedPCO₂ lower (33 ± 1 vs. 36 ± 1 Torr; P = 0.0009), and quadricepsintracellular pH (pH_i) more acid (6.44 ± 0.07 vs. 6.62 ± 0.07; P = 0.004), compared withBLPP_rec. Bloodlactate was modestly increased withBLPP_ex but without a change inarterialized pH. For each subject, pH_i was linearly relatedto minute ventilation during exercise but not to arterialized pH. Thesedata suggest that skeletal muscle hydrogen ion contributes to theexercise ventilatory response.