K+ supplementation increases muscle [Na+-K+-ATPase] and improves extrarenal K+ homeostasis in rats

Bundgaard, Henning, Thomas A. Schmidt, Jim S. Larsen, andKeld Kjeldsen. K⁺supplementation increases muscle[Na⁺-K⁺-ATPase]and improves extrarenal K⁺homeostasis in rats. J. Appl. Physiol.82(4): 1136-1144, 1997.Effects ofK⁺ supplementation (~200 mmolKCl/100 g chow) on plasma K⁺,K⁺ content, andNa⁺-K⁺-adeonsinetriphosphatase(ATPase) concentration([Na⁺-K⁺-ATPase])in skeletal muscles as well as on extrarenalK⁺ clearance were evaluated inrats. After 2 days of K⁺supplementation, hyperkalemia prevailed(K⁺-supplemented vs.weight-matched control animals) [5.1 ± 0.2 (SE) vs. 3.2 ± 0.1 mmol/l, P < 0.05, n = 5-6], and after 4 daysa significant increase in K⁺content was observed in gastrocnemius muscle (104 ± 2 vs. 97 ± 1 µmol/g wet wt, P < 0.05, n = 5-6). After 7 days ofK⁺ supplementation, a significantincrease in[³H]ouabain bindingsite concentration (344 ± 5 vs. 239 ± 8 pmol/g wet wt,P < 0.05, n = 4) was observed in gastrocnemiusmuscle. After 2 wk, increases in plasmaK⁺,K⁺ content, and[³H]ouabain bindingsite concentration in gastrocnemius muscle amounted to 40, 8, and 68%(P < 0.05) above values observed inweight-matched control animals, respectively. The latter change wasconfirmed by K⁺-dependentp-nitrophenyl phosphatase activitymeasurements. Fasting for 1 day reduced plasmaK⁺ andK⁺ content in gastrocnemius musclein rats that had been K⁺supplemented for 2 wk by 3.1 ± 0.3 mmol/l(P < 0.05, n = 5) and 15 ± 2 µmol/g wet wt(P < 0.05, n = 5), respectively. After induction of anesthesia, arterial plasma K⁺was measured during intravenous KCl infusion (0.75 mmolKCl · 100 g bodywt¹ · h¹).The K⁺-supplemented fasted groupdemonstrated a 42% (P < 0.05) lower plasma K⁺ rise, associated with asignificantly higher increase inK⁺ content in gastrocnemius muscleof 7 µmol/g wet wt (P < 0.05, n = 5) compared with their controlanimals. In conclusion, K⁺supplementation increases plasmaK⁺,K⁺ content, and[Na⁺-K⁺-ATPase]in skeletal muscles and improves extrarenalK⁺ clearance capacity.

     

Role of inhibition of nitric oxide production in monocrotaline-induced pulmonary hypertension

Mathew, Rajamma, Elizabeth S. Gloster, T. Sundararajan, Carl I. Thompson, Guillermo A. Zeballos, andMichael H. Gewitz. Role of inhibition of nitric oxide productionin monocrotaline-induced pulmonary hypertension. J. Appl. Physiol. 82(5): 1493-1498, 1997.Monocrotaline (MCT)-induced pulmonary hypertension (PH) isassociated with impaired endothelium-dependent nitric oxide(NO)-mediated relaxation. To examine the role of NO in PH,Sprague-Dawley rats were given a single subcutaneous injection ofnormal saline [control (C)], 80 mg/kg MCT, or the same doseof MCT and a continuous subcutaneous infusion of 2 mg · kg¹ · day¹of molsidomine, a NO prodrug (MCT+MD). Two weeks later, plasma NO₃ levels, pulmonary arterialpressure (Ppa), ratio of right-to-left ventricular weights (RV/LV) toassess right ventricular hypertrophy, and pulmonary histology wereevaluated. The plasma NO₃ level inthe MCT group was reduced to 9.2 ± 1.5 µM(n = 12) vs. C level of 17.7 ± 1.8 µM (n = 8; P < 0.02). In the MCT+MD group,plasma NO₃ level was 12.3 ± 2.0 µM (n = 8). Ppa and RV/LV in theMCT group were increased compared with C [Ppa, 34 ± 3.4 mmHg(n = 6) vs. 19 ± 0.8 mmHg(n = 8) and 0.41 ± 0.01 (n = 9) vs. 0.25 ± 0.008 (n = 8), respectively;P < 0.001]. In the MCT+MDgroup, Ppa and RV/LV were not different when compared with C [19 ± 0.5 mmHg (n = 5) and 0.27 ± 0.01 (n = 9), respectively;P < 0.001 vs. MCT]. Medial wall thickness of lung vessels in the MCT group was increased comparedwith C [31 ± 1.5% (n = 9)vs. 13 ± 0.66% (n = 9);P < 0.001], and MDpartially prevented MCT-induced pulmonary vascular remodeling [22 ± 1.2% (n = 11);P < 0.001 vs. MCT and C].These results indicate that a defect in the availability of bioactive NO may play an important role in the pathogenesis of MCT-induced PH.

     

Creatine supplementation and age influence muscle metabolism during exercise

Young[n = 5, 30 ± 5 (SD) yr] andmiddle-aged (n = 4, 58 ± 4 yr) menand women performed single-leg knee-extension exercise inside a wholebody magnetic resonance system. Two trials were performed 7 days apartand consisted of two 2-min bouts and a third bout continued toexhaustion, all separated by 3 min of recovery.³¹P spectra were used to determinepH and relative concentrations ofP_i, phosphocreatine (PCr), and-ATP every 10 s. The subjects consumed 0.3 g · kg¹ · day¹of a placebo (trial 1) or creatine(trial 2) for 5 days before eachtrial. During the placebo trial, the middle-aged group had a lowerresting PCr compared with the young group (35.0 ± 5.2 vs. 39.5 ± 5.1 mmol/kg, P < 0.05) and alower mean initial PCr resynthesis rate (18.1 ± 3.5 vs. 23.2 ± 6.0 mmol · kg¹ · min¹,P < 0.05). After creatinesupplementation, resting PCr increased 15%(P < 0.05) in the young group and30% (P < 0.05) in the middle-aged group to 45.7 ± 7.5 vs. 45.7 ± 5.5 mmol/kg, respectively. Mean initial PCr resynthesis rate also increased in the middle-aged group(P < 0.05) to a level not differentfrom the young group (24.3 ± 3.8 vs. 24.2 ± 3.2 mmol · kg¹ · min¹).Time to exhaustion was increased in both groups combined after creatinesupplementation (118 ± 34 vs. 154 ± 70 s,P < 0.05). In conclusion, creatinesupplementation has a greater effect on PCr availability andresynthesis rate in middle-aged compared with youngerpersons.

     

Effects of edema on small airway narrowing

Wagner, Elizabeth M. Effects of edema on small airwaynarrowing. J. Appl. Physiol. 83(3):784-791, 1997.Numerous mediators of inflammation have beendemonstrated to cause airway microvascular fluid and proteinextravasation. That fluid extravasation results in airway wall edemaleading to airway narrowing and enhanced reactivity has not beenconfirmed. In anesthetized, ventilated sheep(n = 30), airway vascularfluid extravasation was induced by infusing bradykinin(10⁶ M) through acannulated, blood-perfused bronchial artery. Airway wall edema andluminal narrowing were determined morphometrically. Airway reactivityto methacholine (MCh; 10 µg/ml, intrabronchial artery) was determinedby measuring conducting airway resistance (Raw) by forced oscillation.Raw measurements were made and lung lobes were excised and quick frozenbefore or after a 1-h bradykinin infusion. In 10 airways per lobe(range 0.2- to 2.0-mm relaxed diameter), wall area occupied 32 ± 2% (SE) of the total normalized airway area(n = 9). Bradykinin infusion increasedwall area to 42 ± 5% (P = 0.02);luminal area decreased by <5%; and smooth muscle perimeter, ameasure of smooth muscle constriction, was not altered(n = 5). Raw showed nochange from baseline (1.4 ± 0.4 cmH₂O · l¹ · s)after bradykinin infusion (n = 10).During MCh challenge, Raw increased by 3.2 ± 04 cmH₂O · l¹ · s,and this change did not differ after administration of bradykinin. MChchallenge caused similar decreases in smooth muscle perimeter (10%)and luminal area (72 vs. 68%) before and after bradykinin infusion.However, the time constant of recovery of Raw from MCh constriction wasincreased from control (40 ± 3 s) to 57 ± 10 s after bradykinininfusion (P = 0.03). When lung lobeswere excised at the same time after MCh challenge was terminated(n = 5), luminal area was greaterbefore bradykinin infusion than after (86 vs. 78%;P = 0.007), as was smooth muscleperimeter. The results of this study demonstrate that airway wall edemalimits relaxation after induced constriction rather than enhancingconstriction.

     

Effects of emphysema on diaphragm blood flow during exercise

Chronichyperinflation of the lung in emphysema displaces the diaphragmcaudally, thereby placing it in a mechanically disadvantageous positionand contributing to the increased work of breathing. We tested thehypothesis that total and regional diaphragm blood flows are increasedin emphysema, presumably reflecting an increased diaphragm energeticdemand. Male Syrian Golden hamsters were randomly divided intoemphysema (E; intratracheal elastase 25 units/100 g body wt) andcontrol (C; saline) groups, and experiments were performed 16-20wk later. The regional distribution of blood flow withinthe diaphragm was determined by using radiolabeled microspheres inhamsters at rest and during treadmill exercise (walking at 20 feet/min,20% grade). Consistent with pronounced emphysema, lung volume per unitbody weight was greater in E hamsters (C, 59.3 ± 1.8; E, 84.5 ± 5.0 ml/kg; P < 0.001) and arterialPO₂ was lower both at rest (C, 74 ± 3; E, 59 ± 2 Torr; P < 0.001) and during exercise (C, 93 ± 3; E, 69 ± 4 Torr; P < 0.001). At rest, total diaphragm blood flow was not different between C and Ehamsters (C, 47 ± 4; E, 38 ± 4 ml · min¹ · 100 g¹;P = 0.18). In both C and E hamsters,blood flow at rest was lower in the ventral costal region of thediaphragm than in the dorsal and medial costal regions and the cruraldiaphragm. During exercise in both C and E hamsters, blood flowsincreased more in the dorsal and medial costal regions and in thecrural diaphragm than in the ventral costal region. Total diaphragmblood flow was greater in E hamsters during exercise (C, 58 ± 7; E,90 ± 14 ml · min¹ · 100 g¹;P = 0.03), as a consequence ofsignificantly higher blood flows in the medial and ventral costalregions and crural diaphragm. In addition, exercise-induced increasesin intercostal (P < 0.005) andabdominal (P < 0.05) muscle bloodflows were greater in E hamsters. The finding that diaphragm blood flowwas greater in E hamsters during exercise supports the contention thatemphysema increases the energetic requirements of the diaphragm.

     

Microdialysis ethanol removal reflects probe recovery rather than local blood flow in skeletal muscle

The present study compared the microdialysis ethanoloutflow-inflow technique for estimating blood flow (BF) in skeletalmuscle of humans with measurements by Doppler ultrasound of femoralartery inflow to the limb(BF_FA). The microdialysis probeswere inserted in the vastus lateralis muscle and perfused with a Ringeracetate solution containing ethanol,[2-³H]adenosine (Ado),andD-[¹⁴C(U)]glucose.BF_FA at rest increased from0.16 ± 0.02 to 1.80 ± 0.26 and 4.86 ± 0.53 l/minwith femoral artery infusion of Ado (Ado_FA,i) at 125 and 1,000 µg · min¹ · l¹thigh volume (low dose and high dose, respectively;P < 0.05) and to 3.79 ± 0.37 and6.13 ± 0.65 l/min during one-legged, dynamic, thigh muscle exercisewithout and with high Ado_FA,i,respectively (P < 0.05). The ethanoloutflow-to-inflow ratio (38.3 ± 2.3%) and the probe recoveries(PR) for [2-³H]Ado(35.4 ± 1.6%) and forD-[¹⁴C(U)]glucose(15.9 ± 1.1%) did not change withAdo_FA,i at rest (P = not significant). During exercisewithout and with Ado_FA,i, theethanol outflow-to-inflow ratio decreased(P < 0.05) to a similar level of17.5 ± 3.4 and 20.6 ± 3.2%, respectively(P = not significant), respectively,while the PR increased (P < 0.05) toa similar level (P = not significant)of 55.8 ± 2.8 and 61.2 ± 2.5% for[2-³H]Ado and to 42.8 ± 3.9 and 45.2 ± 5.1% forD-[¹⁴C(U)]glucose.Whereas the ethanol outflow-to-inflow ratio and PR correlated inverselyand positively, respectively, to the changes in BF during muscularcontractions, neither of the ratio nor PR correlated tothe Ado_FA,i-induced BF increase.Thus the ethanol outflow-to-inflow ratio does not represent skeletalmuscle BF but rather contraction-induced changes in molecular transport in the interstitium or over the microdialysis membrane.

     

Head-down-tilt bed rest alters forearm vasodilator and vasoconstrictor responses

To test thehypothesis that head-down-tilt bed rest (HDBR) for 14 days altersvascular reactivity to vasodilatory and vasoconstrictor stimuli, thereactive hyperemic forearm blood flow (RHBF, measured by venousocclusion plethysmography) and mean arterial pressure (MAP, measured byFinapres) responses after 10 min of circulatory arrest were measured ina control trial (n = 20) and whensympathetic discharge was increased by a cold pressor test (RHBF + coldpressor test; n = 10). Vascularconductance (VC) was calculated (VC = RHBF/MAP). In the control trial,peak RHBF at 5 s after circulatory arrest (34.1 ± 2.5 vs.48.9 ± 4.3 ml · 100 ml¹ · min¹)and VC (0.34 ± 0.02 vs. 0.53 ± 0.05 ml · 100 ml¹ · min¹ · mmHg¹)were reduced in the post- compared with the pre-HDBR tests(P < 0.05). Total excess RHBF over 3 min was diminished in the post- compared with the pre-HDBR trial (84.8 vs. 117 ml/100 ml, P < 0.002). Theability of the cold pressor test to lower forearm blood flow was lessin the post- than in the pre-HDBR test(P < 0.05), despite similarincreases in MAP. These data suggest that regulation of vasculardilation and the interaction between dilatory and constrictorinfluences were altered with bed rest.

     

Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity

Skeletal muscle oxidative enzyme capacity is impaired inpatients suffering from emphysema and chronic obstructive pulmonary disease. This effect may result as a consequence of the physiological derangements because of the emphysema condition or, alternatively, as aconsequence of the reduced physical activity level in these patients.To explore this issue, citrate synthase (CS) activity was measured inselected hindlimb muscles and the diaphragm of Syrian Golden hamsters 6 mo after intratracheal instillation of either saline (Con,n = 7) or elastase [emphysema(Emp); 25 units/100 g body weight, n = 8]. Activity level was monitored, and no difference betweengroups was found. Excised lung volume increased with emphysema (Con,1.5 ± 0.3 g; Emp, 3.0 ± 0.3 g,P < 0.002). Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 ± 2.0; Emp, 39.2 ± 0.8 µmol · min¹ · gwet wt¹,P < 0.05) and vastus lateralis (Con,48.5 ± 1.5; Emp, 44.9 ± 0.8 µmol · min¹ · gwet wt¹,P < 0.05) but not in the plantaris(Con, 47.4 ± 3.9; Emp, 48.0 ± 2.1 µmol · min¹ · gwet wt¹,P < 0.05) muscle. In contrast, CSactivity increased in the costal (Con, 61.1 ± 1.8; Emp, 65.1 ± 1.5 µmol · min¹ · gwet wt¹,P < 0.05) and crural (Con, 58.5 ± 2.0; Emp, 65.7 ± 2.2 µmol · min¹ · gwet wt¹, P < 0.05) regions of the diaphragm. These data indicate that emphysema perse can induce decrements in the oxidative capacity of certainnonventilatory skeletal muscles that may contribute to exerciselimitations in the emphysematous patient.

     

Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs

Ventilation during ischemia attenuatesischemia-reperfusion lung injury, but the mechanism is unknown.Increasing tissue cyclic nucleotide levels has been shown to attenuatelung ischemia-reperfusion injury. We hypothesized thatventilation prevented increased pulmonary vascular permeability duringischemia by increasing lung cyclic nucleotide concentrations.To test this hypothesis, we measured vascular permeability and cGMP andcAMP concentrations in ischemic (75 min) sheep lungs that wereventilated (12 ml/kg tidal volume) or statically inflated with the samepositive end-expiratory pressure (5 Torr). The reflection coefficientfor albumin (_alb) was 0.54 ± 0.07 and 0.74 ± 0.02 (SE) in nonventilated and ventilatedlungs, respectively (n = 5, P < 0.05). Filtration coefficientsand capillary blood gas tensions were not different. The effect ofventilation was not mediated by cyclic compression of alveolarcapillaries, because negative-pressure ventilation(n = 4) also was protective (_alb = 0.78 ± 0.09). Thefinal cGMP concentration was less in nonventilated than in ventilatedlungs (0.02 ± 0.02 and 0.49 ± 0.18 nmol/g blood-free dry wt,respectively, n = 5, P < 0.05). cAMP concentrations werenot different between groups or over time. Sodium nitroprussideincreased cGMP (1.97 ± 0.35 nmol/g blood-free dry wt) and_alb (0.81 ± 0.09) innonventilated lungs (n = 5, P < 0.05). Isoproterenol increasedcAMP in nonventilated lungs (n = 4, P < 0.05) but had no effect on_alb. The nitric oxide synthaseinhibitor N^G-nitro-L-arginine methylester had no effect on lung cGMP (n = 9) or _alb(n = 16) in ventilated lungs but didincrease pulmonary vascular resistance threefold(P < 0.05) in perfused sheep lungs (n = 3). These results suggest thatventilation during ischemia prevented an increase in pulmonaryvascular protein permeability, possibly through maintenance of lungcGMP by a nitric oxide-independent mechanism.

     

Rabbit conjunctival epithelium transports fluid, and P2Y22 receptor agonists stimulate Cl{-} and fluid secretion

Rabbit conjunctival epithelium exhibits UTP-dependentCl secretion into the tears. We investigated whetherfluid secretion also takes place. Short-circuit current(I_sc) was 14.9 ± 1.4 µA/cm²(n = 16). Four P2Y₂ purinergic receptoragonists [UTP and the novel compounds INS365, INS306, and INS440(Inspire Pharmaceuticals)] added apically (10 µM) resulted intemporary (~30 min) I_sc increases (88%, 66%,57%, and 28%, respectively; n = 4 each). Importantly, the conjunctiva transported fluid from serosa to mucosa at a rate of6.5 ± 0.7 µl · h¹ · cm² (range2.1-15.3, n = 20). Fluid transport was stimulatedby mucosal additions of 10 µM: 1) UTP, from 7.4 ± 2.3 to 10.7 ± 3.3 µl · h¹ · cm²,n = 5; and 2) INS365, from 6.3 ± 1.0 to 9.8 ± 2.5 µl · h¹ · cm²,n = 5. Fluid transport was abolished by 1 mMouabain (n = 5) and was drastically inhibited by 300 µM quinidine (from 6.4 ± 1.2 to 3.6 ± 1.0 µl · h¹ · cm²,n = 4). We conclude that this epithelium secretes fluidactively and that P2Y₂ agonists stimulate bothCl and fluid secretions.

     

Nitric oxide regulates oxygen uptake and hydrogen peroxide release by the isolated beating rat heart

Isolated rat heart perfused with 1.5-7.5µM NO solutions or bradykinin, which activates endothelial NOsynthase, showed a dose-dependent decrease in myocardial O₂uptake from 3.2 ± 0.3 to 1.6 ± 0.1 (7.5 µM NO, n = 18,P < 0.05) and to 1.2 ± 0.1 µM O₂ · min¹ · gtissue¹ (10 µM bradykinin, n = 10,P < 0.05). Perfused NO concentrations correlated with aninduced release of hydrogen peroxide (H₂O₂) inthe effluent (r = 0.99, P < 0.01). NO markedlydecreased the O₂ uptake of isolated rat heart mitochondria(50% inhibition at 0.4 µM NO, r = 0.99,P < 0.001). Cytochrome spectra in NO-treated submitochondrial particles showed a double inhibition of electron transfer at cytochrome oxidase and between cytochrome b andcytochrome c, which accounts for the effects in O₂uptake and H₂O₂ release. Most NO was bound tomyoglobin; this fact is consistent with NO steady-state concentrationsof 0.1-0.3 µM, which affect mitochondria. In the intact heart,finely adjusted NO concentrations regulate mitochondrial O₂uptake and superoxide anion production (reflected byH₂O₂), which in turn contributes to thephysiological clearance of NO through peroxynitrite formation.

     

Regional measurements of pulmonary edema by using magnetic resonance imaging

Athree-dimensional magnetic resonance imaging (MRI) method to measurepulmonary edema and lung microvascular barrier permeability wasdeveloped and compared with conventional methods in nine mongrel dogs.MRIs were obtained covering the entire lungs. Injury was induced byinjection of oleic acid (0.021-0.048 ml/kg) into a jugularcatheter. Imaging followed for 0.75-2 h. Extravascular lung waterand permeability-related parameters were measured from multiple-indicator dilution curves. Edema was measured as magnetic resonance signal-to-noise ratio (SNR). Postinjury wet-to-dry lung weight ratio was 5.30 ± 0.38 (n = 9). Extravascular lung water increased from 2.03 ± 1.11 to 3.00 ± 1.45 ml/g(n = 9, P < 0.01). Indicatordilution studies yielded parameters characterizing capillary exchangeof urea and butanediol: the product of the square root of equivalentdiffusivity of escape from the capillary and capillary surface area(D^1/2S)and the capillary permeability-surface area product(PS). The ratio ofD^1/2Sfor urea toD^1/2Sfor butanediol increased from 0.583 ± 0.027 to 0.852 ± 0.154 (n = 9, P < 0.05). Whole lung SNR atbaseline, before injury, correlated withD^1/2Sand PS ratios (both P < 0.02). By using rate of SNR change, the mismatch of transcapillaryfiltration flow and lymph clearance was estimated to be0.2-1.8 ml/min. The filtration coefficient was estimated fromthese values. Results indicate that pulmonary edema formation duringoleic acid injury can be imaged regionally and quantified globally, andthe results suggest possible regional quantification by usingthree-dimensional MRI.

     

Energy metabolism in sedentary and active 49-to 70-yr-old women

This study examined differences betweenlong-term exercising (LE) and long-term nonexercising (LNE) women[n = 24; age 56.4 ± 6.2 (SD) yr] for resting metabolic rate (RMR) and energyexpenditure in the free-living state by using doubly labeled water(DLW). There was a statistically significant difference(P = 0.0002) between the 12 LE(94.85 ± 8.44 kJ · kg¹ · day¹)and 12 LNE (81.16 ± 6.62 kJ · kg¹ · day¹)for RMR, but this difference was only marginally significant (P = 0.06) when the data (MJ/day) weresubjected to an analysis of covariance with fat-free mass as thecovariate. The DLW data indicated that the eight most active LE(12.99 ± 3.58 MJ/day) expended significantly(P = 0.01) more energy than did theeight least active LNE (9.30 ± 1.15 MJ/day). Energy expendituresranged from 7.64 to 18.15 MJ/day, but there was no difference(P = 0.96) between the LE and LNE inenergy expenditure during activity that was not designed to eitherimprove or maintain fitness. These cross-sectional data on 49- to70-yr-old women therefore suggest that1) aerobic-type training results ina greater RMR per unit of body mass and also when statistical controlis exerted for the effect of the metabolically active fat-free mass,2) there is a large range in theenergy intake necessary to maintain energy balance, and3) aerobic training does not resultin a compensatory reduction in energy expenditure during the remainderof the day.

     

Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography

Magnetic resonance imaging (MRI) and computerizedtomography (CT) are promising reference methods for quantifying wholebody and regional skeletal muscle mass. Earlier MRI and CTvalidation studies used data-acquisition techniques and data-analysisprocedures now outdated, evaluated anatomic rather than adiposetissue-free skeletal muscle (ATFSM), studied only the relatively largethigh, or found unduly large estimation errors. The aim ofthe present study was to compare arm and leg ATFSM cross-sectional areaestimates (cm²) by usingstandard MRI and CT acquisition and image-analysis methods withcorresponding cadaver estimates. A second objective was to validate MRIand CT measurements of adipose tissue embedded within muscle(interstitial adipose tissue) and surrounding muscle (subcutaneousadipose tissue). ATFSM area (n = 119)by MRI [38.9 ± 22.3 (SD)cm²], CT (39.7 ± 22.8 cm²), and cadaver (39.5 ± 23.0 cm²) were not different(P > 0.001), and both MRI and CTestimates of ATFSM were highly correlated with corresponding cadavervalues [MRI: r = 0.99, SE of estimate (SEE) 3.9 cm²,P < 0.001; and CT:r = 0.99, SEE = 3.8 cm²,P < 0.001].Similarly good results were observed between MRI- and CT-measured vs.cadaver-measured interstitial and subcutaneous adipose tissue. ForMRI-ATFSM the intraobserver correlation for duplicate measurements invivo was 0.99 [SEE = 8.7 cm²(2.9%), P < 0.001]. Thesefindings strongly support the use of MRI and CT as reference methodsfor appendicular skeletal muscle, interstitial and subcutaneous adiposetissue measurement in vivo.

     

Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic reflex

Ray, Chester A., and Keith M. Hume. Neck afferents andmuscle sympathetic activity in humans: implications for the vestibulosympathetic reflex. J. Appl.Physiol. 84(2): 450-453, 1998.We have shownpreviously that head-down neck flexion (HDNF) in humans elicitsincreases in muscle sympathetic nerve activity (MSNA). The purpose ofthis study was to determine the effect of neck muscle afferents onMSNA. We studied this question by measuring MSNA before and after headrotation that would activate neck muscle afferents but not thevestibular system (i.e., no stimulation of the otolith organs orsemicircular canals). After a 3-min baseline period with the head inthe normal erect position, subjects rotated their head to the side(~90°) and maintained this position for 3 min. Head rotation wasperformed by the subjects in both the prone(n = 5) and sitting(n = 6) positions. Head rotation did not elicit changes in MSNA. Average MSNA, expressed asburst frequency and total activity, was 13 ± 1 and 13 ± 1 bursts/min and 146 ± 34 and 132 ± 27 units/min during baselineand head rotation, respectively. There were no significant changes incalf blood flow (2.6 ± 0.3 to 2.5 ± 0.3 ml · 100 ml¹ · min¹;n = 8) and calf vascular resistance(39 ± 4 to 41 ± 4 units; n = 8). Heart rate (64 ± 3 to 66 ± 3 beats/min;P = 0.058) and mean arterial pressure(90 ± 3 to 93 ± 3; P < 0.05)increased slightly during head rotation. Additional neck flexionstudies were performed with subjects lying on their side(n = 5). MSNA, heart rate, and meanarterial pressure were unchanged during this maneuver, which also doesnot engage the vestibular system. HDNF was tested in 9 of the 13 subjects. MSNA was significantly increased by 79 ± 12% (P < 0.001) during HDNF. Thesefindings indicate that neck afferents activated by horizontal neckrotation or flexion in the absence of significant force development donot elicit changes in MSNA. These findings support the concept thatHDNF increases MSNA by the activation of the vestibular system.

     

Enhanced muscle glucose uptake facilitates nitrogen efflux from exercised muscle

The hypothesis that glucose ingestion inthe postexercise state enhances the synthesis of glutamine and alaninein the skeletal muscle was tested. Glucose was infused intraduodenallyfor 150 min (44.5 µmol · kg¹ · min¹)beginning 30 min after a 150-min period of exercise(n = 7) or an equivalent durationsedentary period (n = 10) in18-h-fasted dogs. Prior exercise caused a twofold greater increase inlimb glucose uptake during the intraduodenal glucose infusion compared with uptake in sedentary dogs. Arterial glutamine levels fell graduallywith the glucose load in both groups. Net hindlimb glutamine effluxincreased in response to intraduodenal glucose in exercised but notsedentary dogs (P < 0.05-0.01).Arterial alanine levels, depleted by 50% with exercise, rose withintraduodenal glucose in exercised but not sedentary dogs(P < 0.05-0.01). Net hindlimb alanine efflux also rose in exercised dogs in response to intraduodenal glucose (P < 0.05-0.01),whereas it was not different from baseline in sedentary controls forthe first 90 min of glucose infusion. Beyond this point,it, too, rose significantly. We conclude that oral glucosemay facilitate recovery of muscle from prolonged exercise by enhancingthe removal of nitrogen in the form of glutamine andalanine.

     

Comparisons of two-, three-, and four-compartment models of body composition analysis in men and women

This study compared the traditionaltwo-compartment (fat mass or FM; fat free mass or FFM)hydrodensitometric method of body composition measurement, which isbased on body density, with three (FM, total body water or TBW, fatfree dry mass)- and four (FM, TBW, bone mineral mass or BMM,residual)-compartment models in highly trained men(n = 12), sedentary men(n = 12), highly trained women(n = 12), and sedentary women(n = 12). The means andvariances for the relative body fat (%BF) differences between the two-and three-compartment models [2.2 ± 1.6 (SD) % BF;n = 48] were significantlygreater (P  0.02) than those between the three- and four-compartment models (0.2 ± 0.3% BF;n = 48) for all four groups. Thethree-compartment model is more valid than the two-compartmenthydrodensitometric model because it controls for biological variabilityin TBW, but additional control for interindividual variability in BMMvia the four-compartment model achieves little extra accuracy. Thecombined group (n = 48) exhibited greater (P < 0.001) FFM densities(1.1075 ± 0.0049 g/cm³) thanthe hydrodensitometric assumption of 1.1000 g/cm³, which is based on analysesof three male cadavers aged 25, 35, and 46 yr. This was primarilybecause their FFM hydration (72.4 ± 1.1%;n = 48) was lower(P  0.001) than thehydrodensitometric assumption of 73.72%.

     

Effects of nitric oxide on blood flow distribution and O2 extraction capabilities during endotoxic shock

Zhang, Haibo, Peter Rogiers, Nadia Smail, Ana Cabral,Jean-Charles Preiser, Marie-Odile Peny, and Jean-Louis Vincent.Effects of nitric oxide on blood flow distribution andO₂ extraction capabilities duringendotoxic shock. J. Appl. Physiol.83(4): 1164-1173, 1997.The effects of the nitric oxide (NO)synthase inhibitorN^G-monomethyl-L-arginine(L-NMMA) and the NO donor3-morpholinosydnonimine (SIN-1) were tested in 18 endotoxic dogs. L-NMMA infusion(10 mg · kg¹ · h¹)increased arterial and pulmonary artery pressures and systemic andpulmonary vascular resistances but decreased cardiac index, leftventricular stroke work index, and blood flow to the hepatic, portal,mesenteric, and renal beds. SIN-1 infusion (2 µg · kg¹ · min¹)increased cardiac index; left ventricular stroke work index; andhepatic, portal, and mesenteric blood flow. It did not significantly influence arterial and pulmonary artery pressures but decreased renalblood flow. The critical O₂delivery was similar in the L-NMMA group and in the controlgroup (13.3 ± 1.6 vs. 12.8 ± 3.3 ml · kg¹ · min¹)but lower in the SIN-1 group (9.1 ± 1.8 ml · kg¹ · min¹,both P < 0.05). The criticalO₂ extraction ratio was alsohigher in the SIN-1 group than in the other groups (58.7 ± 10.6 vs.42.2 ± 7.6% in controls, P < 0.05; 43.0 ± 15.5% inL-NMMA group,P = not significant). We conclude thatNO is not implicated in the alterations inO₂ extraction capabilitiesobserved early after endotoxin administration.

     

Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training

McCall, G. E., W. C. Byrnes, A. Dickinson, P. M. Pattany,and S. J. Fleck. Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training.J. Appl. Physiol. 81(5):2004-2012, 1996.Twelve male subjects with recreationalresistance training backgrounds completed 12 wk of intensifiedresistance training (3 sessions/wk; 8 exercises/session; 3 sets/exercise; 10 repetitions maximum/set). All major muscle groupswere trained, with four exercises emphasizing the forearm flexors.After training, strength (1-repetition maximum preacher curl) increasedby 25% (P < 0.05). Magneticresonance imaging scans revealed an increase in the biceps brachiimuscle cross-sectional area (CSA) (from 11.8 ± 2.7 to 13.3 ± 2.6 cm²;n = 8;P < 0.05). Muscle biopsies of thebiceps brachii revealed increases(P < 0.05) in fiber areas for type I(from 4,196 ± 859 to 4,617 ± 1,116 µm²;n = 11) and II fibers (from 6,378 ± 1,552 to 7,474 ± 2,017 µm²;n = 11). Fiber number estimated fromthe above measurements did not change after training (293.2 ± 61.5 × 10³ pretraining; 297.5 ± 69.5 × 10³ posttraining;n = 8). However, the magnitude ofmuscle fiber hypertrophy may influence this response because thosesubjects with less relative muscle fiber hypertrophy, but similarincreases in muscle CSA, showed evidence of an increase in fibernumber. Capillaries per fiber increased significantly(P < 0.05) for both type I(from 4.9 ± 0.6 to 5.5 ± 0.7;n = 10) and II fibers (from 5.1 ± 0.8 to 6.2 ± 0.7; n = 10). Nochanges occurred in capillaries per fiber area or muscle area. Inconclusion, resistance training resulted in hypertrophy of the totalmuscle CSA and fiber areas with no change in estimated fiber number,whereas capillary changes were proportional to muscle fiber growth.

     

Ventricular activation during sympathetic imbalance and its computational reconstruction

We characterized the epicardialactivation sequence during a norepinephrine (NE)-induced ventriculararrhythmia in anesthetized pigs and studied factors that modulatedit. Subepicardial NE infusion caused the QRS complex to invertwithin a single beat (n = 35 animals, 101 observations), and the earliest epicardial activation consistentlyshifted to the randomly located infusion site (n = 14).This preceded right atrial activation, whereas the total ventricularepicardial activation time increased from 20 ± 4 to 50 ± 9 ms (P < 0.01). These events were accompanied by aventricular tachycardia and a drop in left ventricular pressure, whichwere fully reversed after the infusion was stopped. Epicardial pacing at the infusion site mimicked all electrical and hemodynamic changes induced by NE. The arrhythmia was prevented by propranolol and abolished by cardiac sympathetic or vagal nerve stimulation. Focal automaticity was computationally reconstructed using a two-dimensional sheet of 256 × 256 resistively coupled ventricular cells, where calcium handling was abnormally high in the central region. We concludethat adrenergic stimulation to a small region of the ventricle elicitstriggered automaticity and that computational reconstruction implicatescalcium overload. Interventions that reduce spatial inhomogeneities ofintracellular calcium may prevent this type of arrhythmia.