Ronald A. Meyer

Phosphocreatine recovery kinetics following low- and high-intensity exercise in human triceps surae and rat posterior hindlimb muscles

Previous studies have suggested the recovery of phosphocreatine (PCr) after exercise is at least second-order in some conditions. Possible explanations for higher-order PCr recovery kinetics include heterogeneity of oxidative capacity among skeletal muscle fibers and ATP production via glycolysis contributing to PCr resynthesis. Ten human subjects (28 +/- 3 yr; mean +/- SE) performed gated plantar flexion exercise bouts consisting of one contraction every 3 s for 90 s (low-intensity) and three contractions every 3 s for 30 s (high-intensity). In a parallel gated study, the sciatic nerve of 15 adult male Sprague-Dawley rats was electrically stimulated at 0.75 Hz for 5.7 min (low intensity) or 5 Hz for 2.1 min (high intensity) to produce isometric contractions of the posterior hindlimb muscles. [(31)P]-MRS was used to measure relative [PCr] changes, and nonnegative least-squares analysis was utilized to resolve the number and magnitude of exponential components of PCr recovery. Following low-intensity exercise, PCr recovered in a monoexponential pattern in humans, but a higher-order pattern was typically observed in rats. Following high-intensity exercise, higher-order PCr recovery kinetics were observed in both humans and rats with an initial fast component (tau < 15 s) resolved in the majority of humans (6/10) and rats (5/8). These findings suggest that heterogeneity of oxidative capacity among skeletal muscle fibers contributes to a higher-order pattern of PCr recovery in rat hindlimb muscles but not in human triceps surae muscles. In addition, the observation of a fast component following high-intensity exercise is consistent with the notion that glycolytic ATP production contributes to PCr resynthesis during the initial stage of recovery.

Quantitative analysis of the postcontractile blood-oxygenation-level-dependent (BOLD) effect in skeletal muscle

Previous studies show that transient increases in both blood flow and magnetic resonance image signal intensity (SI) occur in human muscle after brief, single contractions, and that the SI increases are threefold larger in physically active compared with sedentary subjects. This study examined the relationship between these transient changes by measuring anterior tibial artery flow (Doppler ultrasound), anterior muscle SI (3T, one-shot echo-planar images, TR/TE = 1,000/35), and muscle blood volume and hemoglobin saturation [near-infrared spectroscopy (NIRS)] in the same subjects after 1-s-duration maximum isometric ankle dorsiflexion contractions. Arterial flow increased to a peak 5.9 ± 0.7-fold above rest (SE, n = 11, range 2.6-10.2) within 7 s and muscle SI increased to a peak 2.7 ± 0.6% (range 0.0-6.0%) above rest within 12 s after the contractions. The peak postcontractile SI change was significantly correlated with both peak postcontractile flow (r = 0.61, n = 11) and with subject activity level (r = 0.63, n = 10) estimated from 7-day accelerometer recordings. In a subset of 7 subjects in which NIRS data acquisition was successful, the peak magnitude of the postcontractile SI change agreed well with SI calculated from the NIRS blood volume and saturation changes (r = 0.80, slope = 1.02, intercept = 0.16), confirming the blood-oxygenation-level-dependent (BOLD) mechanism underlying the SI change. The magnitudes of postcontractile changes in blood saturation and SI were reproduced by a simple one-compartment muscle vascular model that incorporated the observed pattern of postcontractile flow, and which assumed muscle O(2) consumption peaks within 2 s after a brief contraction. The results show that muscle postcontractile BOLD SI changes depend critically on the balance between O(2) delivery and O(2) consumption, both of which can be altered by chronic physical activity.

Gastric gas and fluid emptying assessed by magnetic resonance imaging

Abstract Magnetic resonance imaging (MRI) was used to characterize the volumes and rates of gastric emptying of both liquid and gas following the ingestion of beverages of varying carbonation and carbohydrate levels. Eight subjects drank 800 ml each of four test beverages in a counterbalanced order: water, a non-carbonated carbohydrate-electrolyte solution (NC), a lightly carbonated carbohydrate-electrolyte solution (PC), and a carbonated cola (CC). T2-weighted, echoplanar images (25–30 contiguous slices, 1 cm thick, 256 × 128 matrix, TE = 80, 40 cm FOV) of the abdomen were collected at minutes 3,110, 20, 30, 45, and 60 following beverage ingestion. Images were analyzed for gas and liquid volumes. Water and NC emptied the most rapidly, with half times of 21(3) and 31(3) min, respectively [mean (SE)]. PC emptied significantly slower [47 (6) min] and CC slower yet [107 (8) min]. The carbonation content of the beverage accounted for 84% of the variation in emptying time, whereas carbohydrate content did not account for any significant variation. The gastric gas volume of the CC was higher at 2 min post-ingestion compared with all other drinks; however, the rate of emptying of the gas was the same among all beverages. Significantly greater total gastric volumes (gas+liquid) were associated with the ingestion of CC, and accordingly produced a greater severity of gastric distress, as evaluated with a gastric distress inventory. The high gastric gas volumes (≈600 ml) after ingestion of CC suggested a potential source of error in body composition using standard hydrostatic weighing methods. This prediction was tested in nine additional subjects. Ingestion of 800 ml of CC prior to hydrostatic weighing resulted in a 0.7% underestimate of body density and thus an 11% overestimate of percentage body fat compared to measurements made before beverage consumption.

Measurement of total and unilateral renal blood flow by oblique-angle velocity-encoded 2D-CINE magnetic resonance angiography

Two independent measurements of total renal blood flow (RBF) were made in healthy human subjects (n = 14, mean age 30 yr) by CINE phase-contrast magnetic resonance angiography. RBF, measured by summing the flows measured in the right and left renal arteries, was 1152 +/- 44 ml/min (mean +/- SE). RBF, measured from the difference between supra- and infrarenal abdominal aorta flow, was 1109 +/- 68 ml/min. Regression analysis of the comparison of these two different RBF calculations yielded a correlation coefficient of 0.72 at a p < .05 level of significance. Based on other studies of RBF in normal subjects by para-aminohippuric acid (PAH) clearance, the expected RBF in this subject group was 1211 +/- 62 ml/min. The results indicate that noninvasive measurement of RBF is possible using phase-contrast magnetic resonance methods.

Comparison of oxidative capacity among leg muscles in humans using gated 31P 2-D chemical shift imaging.

In many small animals there are distinct differences in fiber‐type composition among limb muscles, and these differences typically correspond to marked disparities in the oxidative capacities. However, whether there are similar differences in the oxidative capacity among leg muscles in humans is less clear. The purpose of this study was to compare the rate of phosphocreatine (PCr) recovery, a functional in vivo marker of oxidative capacity, in the lateral and medial gastrocnemius, soleus, and the anterior compartment of the leg (primarily the tibialis anterior) of humans. Subjects performed plantar flexion and dorsiflexion gated exercise protocols consisting of 70 sets of three rapid dynamic contractions (<2.86 s) at 20 s intervals (total: 23.3 min). Starting after the sixth set of contractions, 31P 2‐D CSI (8 × 8 matrix, 14–16 cm FOV, 3 cm slice, TR 2.86 s) were acquired via a linear transmit/receive surface coil using a GE 3T Excite System. The CSI data were zero‐filled (32 × 32) and a single FID was produced for each time point in the lateral and medial gastrocnemius, soleus, and anterior compartment. The time constant for PCr recovery was calculated from τ = ‐Δt/ln[D/(D + Q)], where Q is the percentage change in PCr due to contraction during the steady‐state portion of the protocol, D the additional drop in PCr from rest, and Δt is the interval between contractions. The τ of PCr recovery was longer (p < 0.05) in the anterior compartment (32 ± 3 s) than in the lateral (23 ± 2 s) and medial gastrocnemius muscles (24 ± 3 s) and the soleus (22 ± 3 s) muscles. These findings suggest that the oxidative capacity is lower in the anterior compartment than in the triceps surae muscles and is consistent with the notion that fiber‐type phenotypes vary among the leg muscles of humans. Copyright

Short-term high-intensity interval training improves phosphocreatine recovery kinetics following moderate-intensity exercise in humans

Previous studies have shown that high-intensity training improves biochemical markers of oxidative potential in skeletal muscle within a 2-week period. The purpose of this study was to examine the effect of short-term high-intensity interval training on the time constant () of phosphocreatine (PCr) recovery following moderate-intensity exercise, an in vivo measure of functional oxidative capacity. Seven healthy active subjects (age, 21 +/- 4 years; body mass, 69 +/- 11 kg) performed 6 sessions of 4-6 maximal-effort 30 s cycling intervals within a 2-week period, and 7 subjects (age, 24 +/- 5 years; body mass, 80 +/- 15 kg) served as controls. Prior to and following training, phosphorous-31 magnetic resonance spectroscopy (31P-MRS; GE 3T Excite System) was used to measure relative changes in high-energy phosphates and intracellular pH of the quadriceps muscles during gated dynamic leg-extension exercise (3 cycles of 90 s exercise and 5 min of rest). A monoexponential model was used to estimate the of PCr recovery. The of PCr recovery after leg-extension exercise was reduced by 14% with high-intensity interval training (pretraining, 43 +/- 14 s vs. post-training, 37 +/- 15 s; p < 0.05) with no change in the control group (44 +/- 12 s vs. 43 +/- 12 s, respectively; p > 0.05). These findings demonstrate that short-term high-intensity interval training is an effective means of increasing functional oxidative capacity in skeletal muscle.

Force of Voluntary Exercise does not Affect Sensorimotor Cortex Activation as Detected by Functional MRI at 1.5 T

Echo‐planar brain images (1.5 T, 1‐shot GRE, TR/TE=3000/45) were acquired during 30–60 s cycles of repetitive (1.3–1.7 Hz) finger flexion exercise against light (0.24) vs heavy (1.40 kg) weights. In protocols during which exercise was alternated with periods of rest, active voxels were identified in the contralateral motor and somatosensory areas by cross‐correlation against an on–off waveform. However, there was no significant difference between the responses to light vs heavy weights. In a continuous repetitive exercise protocol, in which only the weights were cycled, no force‐correlated voxels were identified. Inasmuch as force‐correlated neurons are known to be present in the primate cortex, the results illustrate a potential limitation of functional MRI studies based on the BOLD effect.

Magnetic resonance measurement of blood flow in peripheral vessels after acute exercise

Velocity-encoded Cine magnetic resonance imaging (MRI) was used to measure blood flow in the anterior tibial artery (AT), posterior tibial artery (PT), and popliteal artery of adult human subjects (mean age 29 yr) before and after 90 s of ankle dorsiflexion exercise. Before exercise, mean flow, peak systolic velocity, and end-diastolic velocity in AT were 8.1 +/- 1.6 (SE, n = 6) ml/min, 26.9 +/- 2.6 cm/s, and -0.6 +/- 0.4 cm/s, respectively. After exercise, mean flow and peak systolic velocity in AT increased by 19-fold and 3-fold, respectively, and end-diastolic velocity increased to 8.7 +/- 1.1 cm/s. Flow in popliteal artery above its bifurcation was similar to the sum of flows in AT and PT, both before and after exercise. Flow in AT declined exponentially after exercise with a mean half-time of 4 min. The results demonstrate the utility of MR phase-encoded flow-velocity measurements for physiological studies of peripheral vascular dynamics after exercise.

Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age

Long-term or untreated diabetes leads to micro- and macrovascular complications. However, there are few tests to evaluate microvascular function. A postcontraction blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) technique was exploited to measure peripheral microvascular function in diabetics and healthy controls matched with respect to age, body mass index, and physical activity. Postcontraction BOLD microvascular response was measured following 1-s maximal isometric ankle dorsiflexion in individuals with diabetes mellitus type I [DMI, n = 15, age 33 ± 3 yr (means ± SE), median diabetes duration = 5.5 yr] and type II (DMII, n = 16, age 45 ± 2 yr, median duration = 2.4 yr); responses were compared with controls (CONI and CONII). Peripheral macrovascular function of the popliteal and tibial arteries was assessed during exercise hyperemia with phase contrast magnetic resonance angiography following repetitive exercise. There were no group differences as a result of diabetes in peripheral microvascular function (peak BOLD response: DMI = 2.04 ± 0.38% vs. CONI = 2.08 ± 0.48%; DMII = 0.93 ± 0.24% vs. CONII = 1.13 ± 0.24%; mean ± SE), but the BOLD response was significantly influenced by age (partial r = -0.384, P = 0.003), supporting its sensitivity as a measure of microvascular function. Eleven individuals had no microvascular BOLD response, including three diabetics with neuropathy and four controls with a family history of diabetes. There were no differences in peripheral macrovascular function between groups when assessing exercise hyperemia or the pulsitility and resistive indexes. Although the BOLD microvascular response was not impaired in early diabetes, these results encourage further investigation of muscle BOLD as it relates to peripheral microvascular health.

Testing models of respiratory control in skeletal muscle.

We examined the relationships between PCr and Pi vs oxygen consumption or twitch rate during stimulation of rat muscle in situ and of perfused cat biceps and soleus muscles. In fast-twitch muscles such as rat gastrocnemius and cat biceps, we found a linear relationship between PCr and oxygen consumption. This result favors thermodynamic regulation of oxygen consumption by cytoplasmic phosphorylation potential rather than kinetic regulation by ADP. PCr changes during stimulation of rat muscle depleted of total creatine or adenine nucleotide were also not consistent with simple kinetic regulation by ADP. In cat soleus (slow-twitch) muscle, the observation of nonexponential PCr changes during stimulation suggested more complicated regulation, possibly involving changes in mitochondrial redox potential.