Vasoconstrictor responses of coronary resistance arteries in exercise-trained pigs

Coronaryresistance arteries isolated from exercise-trained pigs have been shownto exhibit enhanced myogenic reactivity (J. M. Muller, P. R. Myers, andM. Harold Laughlin. J. Appl. Physiol. 75: 2677-2682, 1993). The purpose of this study was to test the hypothesis that exercise training results in enhanced vasoconstrictor responses of these arteries to all vasoconstrictor stimuli[specifically acetylcholine (ACh), endothelin-1 (ET-1), KCl, andthe Ca²⁺ channel-agonist Bay K8644]. Female Yucatan miniature swine were trained (Trn) on amotor-driven treadmill (n = 16) orremained sedentary (Sed, n = 15) for16-20 wk. Arteries 50-120 µm in diameter were isolated andcannulated with micropipettes, and intraluminal pressure was set at 60 cmH₂O throughout experiments.Vasoreactivity was evaluated by examining constrictor responses toincreasing concentrations of ACh(10⁹ to10⁴ M), ET-1(10¹⁰ to10⁸ M), KCl (bathreplacement with isotonic physiological saline solution containing 30 or 80 mM), and Bay K 8644 (10⁹ to10⁶ M). Constricteddiameters are expressed relative to the passive diameter observed after100 µM SNP. All four constrictors produced similar decreases indiameter in arteries from both groups [ACh: 0.52 ± 0.07 (Trn)and 0.54 ± 0,06 (Sed); ET-1: 0.66 ± 0.05 (Trn) and 0.70 ± 0.07 (Sed); KCl: 0.66 ± 0.05 (Trn) and 0.70 ± 0.07 (Sed); Bay K8644: 0.86 ± 0.05 (Trn) and 0.76 ± 0.05 (Sed)]. Present results combined with previous observations indicate that exercise training does not alter vasoconstrictor responses of porcine coronary resistance arteries but specifically increases myogenic reactivity. Thus the underlying cellular mechanisms for myogenic tone are alteredby training but not receptor-mediated mechanisms (ACh and ET-1) norvoltage-gated Ca²⁺ channels (KCland Bay K 8644) in coronary resistance arteries.

     

Short-term exercise training alters responses of porcine femoral and brachial arteries

McAllister, Richard M., and M. Harold Laughlin.Short-term exercise training alters responses of porcine femoraland brachial arteries. J. Appl.Physiol. 82(5): 1438-1444, 1997.The primarypurpose of this study was to test the hypothesis that short-termexercise training enhances endothelium-dependent relaxation of porcinefemoral and brachial arteries. Miniature swine ran on a treadmill for 1 h at 3.5 miles/h, twice daily, for 7 consecutive days (Trn;n = 8). Compared with sedentarycontrols (Sed; n = 7), Trn swineexhibited increased skeletal muscle citrate synthase activity(P < 0.05). Vascular rings ~3 mmin axial length were prepared from segments of femoral and brachialarteries, and responses to vasoactive agents were determined in vitro.Sensitivity to bradykinin (BK) was enhanced in brachial vascular ringsfrom Trn swine compared with those from Sed swine, as indicated bylower concentration of vasorelaxing agent eliciting 50% of maximalresponse values [Sed, 8.63 ± 0.09 (log M); Trn, 9.07 ± 0.13; P < 0.05]. Thisdifference between groups was preserved in brachial rings in whichformation of nitric oxide and vasodilator prostaglandins were inhibited[Sed, 8.57 ± 0.17 (log M); Trn, 8.97 ± 0.13;P < 0.05]. Sensitivity to BKwas not different between Sed and Trn in femoral arterial rings.Relaxation responses to the calcium ionophore A-23187 and sodiumnitroprusside were not altered with training. Femoral and brachialarterial rings from Trn swine, compared with those from Sed swine,exhibited augmented vasocontraction across a range of concentrationsand increased sensitivity to norepinephrine (allP < 0.05). These findings indicatethat responses of porcine femoral and brachial arteries change inresponse to short-term training. Together with findings from previousstudies involving longer term training, our data suggest that vascular adaptations may differ at different time points during long-term endurance exercise training.

     

Enhancement of intestinal water absorption and sodium transport by glycerol in rats

Wapnir, Raul A., Maria C. Sia, and Stanley E. Fisher.Enhancement of intestinal water absorption and sodium transport byglycerol in rats. J. Appl. Physiol.81(6): 2523-2527, 1996.Glycerol (Gly) is a hydrophilic,absorbable, and energy-rich solute that could make water absorptionmore efficient. We investigated the use of Gly in a high-energybeverage containing corn syrup (CS) by using a small intestineperfusion procedure in the rat, an approach shown earlier to providegood preclinical information. The effectiveness of several formulationswith Gly and CS was compared with commercial products and toexperimental formulas where Gly substituted for glucose (Glc). TheCS-Gly combination was more effective than preparations on the marketcontaining sucrose and Glc-fructose syrups (G-P and G-L, respectively)in maintaining a net water absorption balance in the test jejunal segment [CS-Gly = 0.021 ± 0.226, G-L = 1.516 ± 0.467, and G-P = 0.299 ± 0.106 (SE)µl ^· min^{1 ·} cm¹(P = 0.0113)] and in reducingsodium release into the lumen [CS-Gly = 133.2 ± 16.2, G-L = 226.7 ± 25.2, and G-P = 245.6 ± 23.4 nmol ^· min^{1 ·} cm¹(P = 0.0022)]. In otherpreparations, at equal CS concentrations (60 and 80 g/l, respectively),Gly clearly improved net water absorption over a comparableGlc-containing product [CS60-Gly = 0.422 ± 0.136 and CS80-Gly = 0.666 ± 0.378 vs. CS60-Glc = 0.282 ± 0.200 andCS80-Glc = 1.046 ± 0.480 µl ^· min^{1 ·} cm¹(P = 0.0019)]. On the basis ofthe data of this rat intestine perfusion model, Gly could be a usefulingredient in energy-rich beverages and might enhance fluid absorptionin humans.

     

Muscle glycogen accumulation after endurance exercise in trained and untrained individuals

Hickner, R. C., J. S. Fisher, P. A. Hansen, S. B. Racette,C. M. Mier, M. J. Turner, and J. O. Holloszy. Muscle glycogen accumulation after endurance exercise in trained and untrained individuals. J. Appl. Physiol. 83(3):897-903, 1997.Muscle glycogen accumulation was determined in sixtrained cyclists (Trn) and six untrained subjects (UT) at 6 and either48 or 72 h after 2 h of cycling exercise at ~75% peakO₂ uptake(O_{2 peak}), which terminated with five 1-min sprints. Subjects ate 10 gcarbohydrate · kg¹ · day¹for 48-72 h postexercise. Muscle glycogen accumulation averaged 71 ± 9 (SE) mmol/kg (Trn) and 31 ± 9 mmol/kg (UT) during the first 6 h postexercise (P < 0.01) and 79 ± 22 mmol/kg (Trn) and 60 ± 9 mmol/kg (UT) between 6 and 48 or 72 h postexercise (not significant). Muscle glycogenconcentration was 164 ± 21 mmol/kg (Trn) and 99 ± 16 mmol/kg(UT) 48-72 h postexercise (P < 0.05). Muscle GLUT-4 content immediately postexercise was threefoldhigher in Trn than in UT (P < 0.05)and correlated with glycogen accumulation rates (r = 0.66, P < 0.05). Glycogen synthase in theactive I form was 2.5 ± 0.5, 3.3 ± 0.5, and 1.0 ± 0.3 µmol · g¹ · min¹in Trn at 0, 6, and 48 or 72 h postexercise, respectively;corresponding values were 1.2 ± 0.3, 2.7 ± 0.5, and 1.6 ± 0.3 µmol · g¹ · min¹in UT (P < 0.05 at 0 h). Plasmainsulin and plasma C-peptide area under the curve were lower in Trnthan in UT over the first 6 h postexercise(P < 0.05). Plasma creatine kinaseconcentrations were 125 ± 25 IU/l (Trn) and 91 ± 9 IU/l (UT)preexercise and 112 ± 14 IU/l (Trn) and 144 ± 22 IU/l(UT; P < 0.05 vs.preexercise) at 48-72 h postexercise (normal: 30-200 IU/l).We conclude that endurance exercise training results in an increasedability to accumulate muscle glycogen after exercise.

     

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.

     

Training-induced alterations of carbohydrate metabolism in women: women respond differently from men

We examined the hypothesis that glucose flux wasdirectly related to relative exercise intensity both beforeand after a 12-wk cycle ergometer training program [5days/wk, 1-h duration, 75% peakO₂ consumption(O_{2 peak})] inhealthy female subjects (n = 17; age23.8 ± 2.0 yr). Two pretraining trials (45 and 65% of O_{2 peak})and two posttraining trials [same absolute workload (65% of oldO_{2 peak})and same relative workload (65% of new O_{2 peak})] wereperformed on nine subjects by using a primed-continuous infusion of[1-¹³C]- and[6,6-²H]glucose.Eight additional subjects were studied by using[6,6-²H]glucose.Subjects were studied postabsorption for 90 min of rest and 1 h ofcycling exercise. After training, subjects increased O_{2 peak} by 25.2 ± 2.4%. Pretraining, the intensity effect on glucose kinetics wasevident between 45 and 65% ofO_{2 peak} with rates ofappearance (R_a: 4.52 ± 0.25 vs. 5.53 ± 0.33 mg · kg¹ · min¹),disappearance (R_d: 4.46 ± 0.25 vs. 5.54 ± 0.33 mg · kg¹ · min¹),and oxidation (R_ox: 2.45 ± 0.16 vs. 4.35 ± 0.26 mg · kg¹ · min¹)of glucose being significantly greater(P  0.05) in the 65% thanin the 45% trial. Training reducedR_a (4.7 ± 0.30 mg · kg¹ · min¹),R_d (4.69 ± 0.20 mg · kg¹ · min¹),and R_ox (3.54 ± 0.50 mg · kg¹ · min¹)at the same absolute workload (P  0.05). When subjects were tested at the same relative workload,R_a,R_d, andR_ox were not significantlydifferent after training. However, at both workloads after training,there was a significant decrease in total carbohydrate oxidation asdetermined by the respiratory exchange ratio. These results show thefollowing in young women: 1)glucose use is directly related to exercise intensity;2) training decreasesglucose flux for a given power output;3) when expressed asrelative exercise intensity, training does not affect the magnitude ofblood glucose flux during exercise; but4) training does reduce totalcarbohydrate oxidation.

     

Changes in maximum oxygen uptake during prolonged training, overtraining, and detraining in horses

Tyler, Catherine M., Lorraine C. Golland, David L. Evans,David R. Hodgson, and Reuben J. Rose. Changes in maximum oxygenuptake during prolonged training, overtraining, and detraining inhorses. J. Appl. Physiol. 81(5):2244-2249, 1996.Thirteen standardbred horses were trained asfollows: phase 1 (endurance training, 7 wk),phase 2 (high-intensity training, 9 wk),phase 3 (overload training, 18 wk), andphase 4 (detraining, 12 wk). Inphase 3, the horses were divided intotwo groups: overload training (OLT) and control (C). The OLT groupexercised at greater intensities, frequencies, and durations than groupC. Overtraining occurred after 31 wk of training and was defined as asignificant decrease in treadmill run time in response to astandardized exercise test. In the OLT group, there was a significantdecrease in body weight (P < 0.05).From pretraining values of 117 ± 2 (SE)ml ^· kg^{1 ·} min¹,maximal O₂ uptake(O_{2 max}) increased by15% at the end of phase 1, and when signs of overtraining werefirst seen in the OLT group,O_{2 max} was 29%higher (151 ± 2 ml ^· kg^{1 ·} min¹in both C and OLT groups) than pretraining values. There was nosignificant reduction inO_{2 max} until after 6 wk detraining whenO_{2 max} was 137 ± 2 ml ^· kg^{1 ·} min¹.By 12 wk detraining, meanO_{2 max} was134 ± 2 ml ^· kg^{1 ·} min¹,still 15% above pretraining values. When overtraining developed, O_{2 max} was notdifferent between C and OLT groups, but maximal values forCO₂ production (147 vs. 159 ml ^· kg^{1 ·} min¹)and respiratory exchange ratio (1.04 vs. 1.11) were lower in the OLTgroup. Overtraining was not associated with a decrease inO_{2 max} and, afterprolonged training, decreases inO_{2 max} occurredslowly during detraining.

     

Training improves endothelium-dependent vasodilation in resistance vessels of patients with heart failure

Katz, Stuart D., Jeannette Yuen, Rachel Bijou, and ThierryH. LeJemtel. Training improves endothelium-dependent vasodilation in resistance vessels of patients with heart failure.J. Appl. Physiol. 82(5):1488-1492, 1997.The effects of physical training onendothelium-dependent vasodilation in skeletal muscle resistance vessels were investigated in patients with heart failure. Forearm bloodflows(ml · min¹ · 100 ml¹) in response tobrachial arterial administration of acetylcholine (5 × 10⁵ and 5 × 10⁴ M at 1 ml/min) andnitroglycerin (5 × 10⁶ and 5 × 10⁵ M at 1 ml/min) weredetermined by strain-gauge venous occlusion plethysmography before andafter 8 wk of daily handgrip exercise in 12 patients with chronic heartfailure. After 8 wk of daily handgrip exercise, the vasodilatoryresponses to acetylcholine significantly increased from pretrainingvalues, i.e., 16.6 ± 2.0 vs. 8.6 ± 1.3 ml · min¹ · 100 ml¹(P < 0.05) and 27.5 ± 1.5 vs. 14.6 ± 1.7 ml · min¹ · 100 ml¹(P < 0.05), respect- ively,whereas the vasodilatory responses to nitroglycerin did notchange. Handgrip exercise training appears to specificallyenhance endothelium-dependent vasodilation in the forearm skeletalmuscle circulation of patients with heart failure.

     

Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

Watchko, Jon F., Monica J. Daood, Gary C. Sieck, John J. LaBella, Bill T. Ameredes, Alan P. Koretsky, and BeWieringa. Combined myofibrillar and mitochondrialcreatine kinase deficiency impairs mouse diaphragm isotonic function.J. Appl. Physiol. 82(5): 1416-1423, 1997.Creatine kinase (CK) is an enzyme central to cellular high-energy phosphate metabolism in muscle. To characterize the physiological role of CK in respiratory muscle during dynamic contractions, we compared the force-velocity relationships, power, andwork output characteristics of the diaphragm (Dia) from mice withcombined myofibrillar and sarcomeric mitochondrial CK deficiency (CK[/]) with CK-sufficient controls (Ctl).Maximum velocity of shortening was significantly lower inCK[/] Dia (14.1 ± 0.9 L_o/s,where L_o isoptimal fiber length) compared with Ctl Dia (17.5 ± 1.1 L_o/s)(P < 0.01). Maximum power wasobtained at 0.4-0.5 tetanic force in both groups; absolute maximumpower (2,293 ± 138 W/m²) andwork (201 ± 9 J/m²) werelower in CK[/] Dia compared with Ctl Dia(2,744 ± 146 W/m² and 284 ± 26 J/m², respectively)(P < 0.05). The ability ofCK[/] Dia to sustain shortening duringrepetitive isotonic activation (75 Hz, 330-ms duration repeated eachsecond at 0.4 tetanic force load) was markedly impaired, withCK[/] Dia power and work declining to zero by 37 ± 4 s, compared with 61 ± 5 s in Ctl Dia. We conclude that combined myofibrillar and sarcomeric mitochondrial CK deficiency profoundly impairs Dia power and work output, underscoring the functional importance of CK during dynamic contractions in skeletal muscle.

     

Effect of sprint cycle training on activities of antioxidant enzymes in human skeletal muscle

Hellsten, Ylva, Fred S. Apple, and Bertil Sjödin.Effect of sprint cycle training on activities of antioxidantenzymes in human skeletal muscle. J. Appl.Physiol. 81(4): 1484-1487, 1996.The effect ofintermittent sprint cycle training on the level of muscle antioxidantenzyme protection was investigated. Resting muscle biopsies, obtainedbefore and after 6 wk of training and 3, 24, and 72 h after the finalsession of an additional 1 wk of more frequent training, were analyzedfor activities of the antioxidant enzymes glutathione peroxidase (GPX),glutathione reductase (GR), and superoxide dismutase (SOD). Activitiesof several muscle metabolic enzymes were determined to assess the effectiveness of the training. After the first 6-wk training period, nochange in GPX, GR, or SOD was observed, but after the 7th week oftraining there was an increase in GPX from 120 ± 12 (SE) to 164 ± 24 µmol ^· min^{1 ·} gdry wt¹(P < 0.05) and in GR from 10.8 ± 0.8 to 16.8 ± 2.4 µmol ^· min^{1 ·} gdry wt¹(P < 0.05). There was no significantchange in SOD. Sprint cycle training induced a significant(P < 0.05) elevation in the activity of phosphofructokinase and creatine kinase, implying an enhanced anaerobic capacity in the trained muscle. The present studydemonstrates that intermittent sprint cycle training that induces anenhanced capacity for anaerobic energy generation also improves thelevel of antioxidant protection in the muscle.

     

Training-induced alterations of glucose flux in men

Friedlander, Anne L., Gretchen A. Casazza, Michael A. Horning, Melvin J. Huie, and George A. Brooks. Training-induced alterations of glucose flux in men. J. Appl.Physiol. 82(4): 1360-1369, 1997.We examined thehypothesis that glucose flux was directly related to relative exerciseintensity both before and after a 10-wk cycle ergometer trainingprogram in 19 healthy male subjects. Two pretraining trials [45and 65% of peak O₂ consumption(O_{2 peak})] andtwo posttraining trials (same absolute and relative intensities as 65%pretraining) were performed for 90 min of rest and 1 h of cyclingexercise. After training, subjects increasedO_{2 peak} by9.4 ± 1.4%. Pretraining, the intensity effect on glucose kinetics was evident with rates of appearance(R_a; 5.84 ± 0.23 vs. 4.73 ± 0.19 mg · kg¹ · min¹),disappearance (R_d; 5.78 ± 0.19 vs. 4.73 ± 0.19 mg · kg¹ · min¹),oxidation (R_ox; 5.36 ± 0.15 vs. 3.41 ± 0.23 mg · kg¹ · min¹),and metabolic clearance (7.03 ± 0.56 vs. 5.20 ± 0.28 ml · kg¹ · min¹)of glucose being significantly greater(P  0.05) in the 65% than the 45%O_{2 peak} trial. WhenR_d was expressed as a percentage of total energy expended per minute(R_{d E}), there was nodifference between the 45 and 65% intensities. Training did reduceR_a (4.63 ± 0.25),R_d (4.65 ± 0.24),R_ox (3.77 ± 0.43), andR_{d E} (15.30 ± 0.40 to12.85 ± 0.81) when subjects were tested at the same absolute workload (P  0.05). However, whenthey were tested at the same relative workload,R_a,R_d, andR_{d E} were not different,although R_ox was lowerposttraining (5.36 ± 0.15 vs. 4.41 ± 0.42, P  0.05). These results show1) glucose use is directly relatedto exercise intensity; 2) trainingdecreases glucose flux for a given power output;3) when expressed as relativeexercise intensity, training does not affect the magnitude of bloodglucose use during exercise; 4)training alters the pathways of glucose disposal.

     

Diffusional permeability of rabbit mesothelium

Diffusional permeability (P) to sucrose(P_suc) andNa⁺(P_Na⁺)was determined in specimens of rabbit sternal parietal pericardium,which may be obtained without stripping. Specimens were mounted in anUssing apparatus with ³H-labeledsucrose and²²Na⁺in a luminal (L) or interstitial (I) chamber.P_suc was 2.16 ± 0.44 for LI and 2.63 ± 0.45 (SE) × 10⁵ cm/s for IL,i.e., ~10 times smaller than that previously obtained in strippedspecimens of pleura despite the similarity of intercellular junctionsin pericardium and pleural mesothelium of various species. Thesefindings suggest that previousP_suc wasoverestimated because stripping damages the mesothelium.P_Na⁺ (×10⁵ cm/s) was 7.07 ± 0.71 for LI and 7.37 ± 0.69 × 10⁵ cm/s for IL.Measurements were also done with phospholipids, which are adsorbed onthe luminal side of mesothelium in vivo. With phospholipids in L,P_suc was 0.75 ± 0.10 and 0.65 ± 0.08 andP_Na⁺was 3.80 ± 0.32 and 3.76 ± 0.15 × 10⁵ cm/s for LI andIL, respectively, i.e., smaller than without phospholipids.With phospholipids in I (where they are not adsorbed), P_suc (2.33 ± 0.42 × 10⁵ cm/s) andP_Na⁺(7.01 ± 0.45 × 10⁵ cm/s) were similar tothose values without phospholipids. Hence, adsorbed phospholipidsdecrease P of mesothelium. If themesothelium were scraped away from the specimen,P_suc of theconnective tissue would be 13.2 ± 0.76 × 10⁵ cm/s.P_suc of themesothelium, computed fromP_suc of theunscraped and scraped specimens, corrected for the effect of unstirredlayers (2.54 and 19.4 × 10⁵ cm/s, respectively),was 2.92 and 0.74 × 10⁵ cm/s without and withphospholipids, respectively. Hence, most of the resistance to diffusionof the pericardium is provided by the mesothelium.

     

Contraction-induced increase in Vmax of palmitate uptake and oxidation in perfused skeletal muscle

To evaluate the effects of contractions on thekinetics of uptake and oxidation of palmitate in a physiological musclepreparation, rat hindquarters were perfused with glucose (6 mmol/l),albumin-bound [1-¹⁴C]palmitate, andvarying amounts of albumin-bound palmitate (200-2,200 µmol/l) atrest and during muscle contractions. When plotted against the unboundpalmitate concentration, palmitate uptake and oxidation displayedsimple Michaelis-Menten kinetics with estimated maximal velocity(V_max)and Michaelis-Menten constant(K_m) values of42.8 ± 3.8 (SE)nmol · min¹ · g¹and 13.4 ± 3.4 nmol/l for palmitate uptake and 3.8 ± 0.4 nmol · min¹ · g¹and 8.1 ± 2.9 nmol/l for palmitate oxidation, respectively, at rest.Whereas muscle contractions increased theV_maxfor both palmitate uptake and oxidation to 91.6 ± 10.1 and 16.5 ± 2.3 nmol · min¹ · g¹,respectively, theK_m remainedunchanged.V_maxand K_m estimates obtained from Hanes-Woolf plots (substrate concentration/velocity vs.substrate concentration) were not significantly different. In theresting perfused hindquarter, an increase in palmitate delivery from31.9 ± 0.9 to 48.7 ± 1.2 µmol · g¹ · h¹by increasing perfusate flow was associated with a decrease in thefractional uptake of palmitate so that the rates of uptake andoxidation of palmitate remained unchanged. It is concluded that therates of uptake and oxidation of long-chain fatty acids (LCFA) saturatewith an increase in the concentration of unbound LCFA in perfusedskeletal muscle and that muscle contractions, but not an increase inplasma flow, increase theV_maxfor LCFA uptake and oxidation. The data are consistent with the notion that uptake of LCFA in muscle may be mediated in part by a transport system.

     

Increased compliance in diaphragm muscle of the cardiomyopathic Syrian hamster

We investigatedthe hypothesis that diaphragm compliance was abnormal incardiomyopathic Syrian hamsters (CSH), an experimental model ofmyopathy. The passive elastic properties of isolated diaphragm muscleswere analyzed at both the muscle and sarcomere levels. We used thefollowing passive exponential relationship between stress () andstrain ():  = (E_o/)(e  1), where E_o is the initialelastic modulus and  is the stiffness constant. Immunocytochemistryprocedures were used to analyze the distribution of two key elasticcomponents of muscle, extracellular collagen and intracellular titinelastic components, as well as the extracellular matrix glycoproteinlaminin. Muscle and sarcomere values of  were nearly twofold lowerin CSH (8.7 ± 1.9 and 8.3 ± 1.4, respectively) than in controlanimals (19.7 ± 1.7 and 16.8 ± 2.1, respectively)(P < 0.01 for each). Compared withcontrols, E_o was higher in CSH.Sarcomere slack length was significantly longer in CSH than in controlanimals (2.1 ± 0.1 vs. 1.9 ± 0.1 µm,P < 0.05). The surface area ofcollagen I was significantly larger in CSH (17.4 ± 1.8%) than incontrol animals (12.4 ± 0.7%, P < 0.05). There was no change in the distribution of titin or lamininlabelings between the groups. These results demonstrate increaseddiaphragm compliance in cardiomyopathic hamsters. The increase in CSHdiaphragm compliance was observed despite an increase in the surfacearea of collagen and was not associated with an abnormal distributionof titin or laminin.

     

Bioenergetics of contracting skeletal muscle after partial reduction of blood flow

The purpose ofthis study was to examine the bioenergetics and regulation ofO₂ uptake(O₂) and force productionin contracting muscle when blood flow was moderately reduced during asteady-state contractile period. Canine gastrocnemius muscle(n = 5) was isolated, and 3-minstimulation periods of isometric, tetanic contractions were elicitedsequentially at rates of 0.25, 0.33, and 0.5 contractions/s (Hz)immediately followed by a reduction of blood flow [ischemic (I)condition] to 46 ± 3% of the value obtained at 0.5 Hz with normal blood flow. TheO₂ of thecontracting muscle was significantly (P < 0.05) reduced during the Icondition [6.5 ± 0.8 (SE) ml · 100 g¹ · min¹]compared with the same stimulation frequency with normal flow (11.2 ± 1.5 ml · 100 g¹ · min¹),as was the tension-time index (79 ± 12 vs. 123 ± 22 N · g¹ · min¹,respectively). The ratio ofO₂ to tension-time indexremained constant throughout all contraction periods. Musclephosphocreatine concentration, ATP concentration, and lactate effluxwere not significantly different during the I condition compared withthe 0.5-Hz condition with normal blood flow. However, at comparable rates of O₂ andtension-time index, muscle phosphocreatine concentration and ATPconcentration were significantly less during the I condition comparedwith normal-flow conditions. These results demonstrate that, in thishighly oxidative muscle, the normal balance ofO₂ supply to force output wasmaintained during moderate ischemia by downregulation of forceproduction. In addition,1) the minimal disruption inintracellular homeostasis after the initiation of ischemia waslikely a result of steady-state metabolic conditions having alreadybeen activated, and 2) thedifference in intracellular conditions at comparable rates ofO₂ and tension-time index between the normal flow and I condition may have been due to altered intracellular O₂ tension.

     

Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure

To simulate theimmediate hemodynamic effect of negative intrathoracic pressure duringobstructive apneas in congestive heart failure (CHF), without inducingconfounding factors such as hypoxia and arousals from sleep, eightawake patients performed, at random, 15-s Mueller maneuvers (MM) attarget intrathoracic pressures of 20 (MM 20) and40 cmH₂O (MM 40),confirmed by esophageal pressure, and 15-s breath holds, as apneic timecontrols. Compared with quiet breathing, at baseline, before theseinterventions, the immediate effects [first 5 cardiac cycles(SD), P values refer to MM 40compared with breath holds] of apnea, MM 20, and MM 40 were, for left ventricular (LV) systolic transmural pressure (Ptm), 1.0 ± 1.9, 7.2 ± 3.5, and 11.3 ± 6.8 mmHg(P < 0.01); for systolic bloodpressure (SBP), 2.9 ± 2.6, 5.5 ± 3.4, and 12.1 ± 6.8 mmHg (P < 0.01); and forstroke volume (SV) index, 0.4 ± 2.8, 4.1 ± 2.8, and6.9 ± 2.3 ml/m²(P < 0.001), respectively.Corresponding values over the last five cardiac cycles were for LVPtm6.4 ± 4.4, 5.4 ± 6.6, and 4.5 ± 9.1 mmHg (P < 0.01); for SBP6.9 ± 4.2, 8.2 ± 7.7, and 24.2 ± 6.9 mmHg (P < 0.01); and for SVindex 0.4 ± 2.1, 5.2 ± 2.8, and 9.2 ± 4.8 ml/m²(P < 0.001), respectively.Thus, in CHF patients, the initial hemodynamic response to thegeneration of negative intrathoracic pressure includes an immediateincrease in LV afterload and an abrupt fall in SV. The magnitude ofresponse is proportional to the intensity of the MM stimulus. By theend of a 15-s MM 40, LVPtm falls below baseline values, yet SVand SBP do not recover. Thus, when 40cmH₂O intrathoracic pressure issustained, additional mechanisms, such as a drop in LV preload due toventricular interaction, are engaged, further reducing SV. The neteffect of MM 40 was a 33% reduction in SV index (from 27 to 18 ml/min²), and a 21% reductionin SBP (from 121 to 96 mmHg). Obstructive apneas can have adverseeffects on systemic and, possibly, coronary perfusion in CHF throughdynamic mechanisms that are both stimulus and timedependent.

     

Exercise-associated hyponatremia in Alaskan sled dogs: urinary and hormonal responses

Hinchcliff, K. W., G. A. Reinhart, J. R. Burr, R. A. Swenson. Exercise-associated hyponatremia in Alaskansled dogs: urinary and hormonal responses. J. Appl.Physiol. 83(3): 824-829, 1997.Exercise-associated hyponatremia occurs in horses and humans, both species that sweat, and in sled dogs, which do not sweat. Toinvestigate the mechanism of exercise-associated hyponatremia in sleddogs, we measured water turnover, serum electrolyte concentrations andosmolality, plasma renal hormone concentrations, and urine compositionof 12 fit Alaskan sled dogs before, during, and after a 490-km sled dograce (Ex group). Water turnover and serum electrolyte concentrationswere measured in six similarly fit dogs that did not run (Sed group).Water turnover was significantly larger(P < 0.001) in Ex [190 ± 19 (SD)ml · kg¹ · day¹]than in Sed dogs (51 ± 13 ml · kg¹ · day¹).There were significant (P < 0.001)decreases in serum sodium concentration (from 148.6 ± 2.8 to 139.7 ± 1.9 mmol/l) and osmolality (from 306 ± 9 to 296 ± 5 mosmol/kgH₂O) of Ex, but not Sed,dogs during the race. Plasma concentrations of arginine vasopressin decreased, whereas aldosterone and plasma renin activity increased significantly (P < 0.01) during therace. Urine osmolality was unchanged, whereas urine sodium, potassium,and chloride concentrations decreased significantly(P < 0.05) and urine ureaconcentration increased (P = 0.06).These results demonstrate increased water turnover associated withhyponatremia and renal sodium conservation with maintained high urineosmolality in exercising Alaskan sled dogs.

     

Effects of vigorous exercise training and beta -agonist administration on bone response to hindlimb suspension

Bloomfield, Susan A., Beverly E. Girten, and Steven E. Weisbrode. Effects of vigorous exercise training and -agonist administration on bone response to hindlimb suspension.J. Appl. Physiol. 83(1):172-178, 1997.The effectiveness of dobutamine (Dob) inpreventing bone loss during 14 days of hindlimb suspension (Sus) wastested in exercise-trained (Ex; n = 25) and sedentary (Sed; n = 22) rats(age 155 days). One-half of each group was given Dob (2 mg · kg¹ · day¹)or saline (Sal). Histomorphometric measurements at midfemur revealed a17% smaller cortical bone area (CBA) and a 32% lower periostealmineral apposition rate (MAR) in suspended vs. nonsuspended Sed/Salrats. Dob abolished this decline in CBA in Sed/Sus rats, probably via an attenuation of the decrease in periosteal MAR; similarbut nonsignificant effects on cross-sectional moment of inertia wereobserved. Nonsuspended Ex rats had no change in bone CBA when CBA isindexed to body weight. Sus appeared to uncouple the relationshipbetween soleus weight and CBA. Dob attenuated the 43% decline insoleus weight after Sus in Ex but not in Sed rats. In summary, vigorousEx before Sus does not affect loss of bone mass due to unloading; Dobeffectively maintains CBA in Sed rats subjected to suspension.

     

Human skeletal muscle carnitine palmitoyltransferase I activity determined in isolated intact mitochondria

This study was designed to compare theactivity of skeletal muscle carnitine palmitoyltransferase I (CPT I) intrained and inactive men (n = 14) andwomen (n = 12). CPT Iactivity was measured in intact mitochondria, isolated from needlebiopsy vastus lateralis muscle samples (~60 mg). The variability ofCPT I activity determined on two biopsy samples from the same leg onthe same day was 4.4, whereas it was 7.0% on two biopsy samples fromthe same leg on different days. The method was sensitive to the CPT Iinhibitor malonyl-CoA (88% inhibition) and therefore specific for CPTI activity. The mean CPT I activity for all 26 subjects was 141.1 ± 10.6 µmol · min¹ · kgwet muscle (wm)¹ and wasnot different when all men vs. all women (140.5 ± 15.7 and 142.2 ± 14.5 µmol · min¹ · kgwm¹, respectively) were compared. However, CPT Iactivity was significantly higher in trained vs. inactive subjects forboth men (176.2 ± 21.1 vs. 104.1 ± 13.6 µmol · min¹ · kgwm¹) and women (167.6 ± 14.1 vs. 91.2 ± 9.5 µmol · min¹ · kgwm¹). CPT I activity was also significantly correlatedwith citrate synthase activity (all subjects,r = 0.76) and maximal oxygen consumption expressed in milliliters per kilogram per minute (all subjects, r = 0.69). Theresults of this study suggest that CPT I activity can be accurately andreliably measured in intact mitochondria isolated from human musclebiopsy samples. CPT I activity was not affected by gender, and higheractivities in aerobically trained subjects appeared to be the result ofincreased mitochondrial content in both men and women.

     

Combined heart rate and activity improve estimates of oxygen consumption and carbon dioxide production rates

Moon, Jon K., and Nancy F. Butte. Combined heart rateand activity improve estimates of oxygen consumption and carbon dioxideproduction rates. J. Appl. Physiol.81(4): 1754-1761, 1996.Oxygen consumption(O₂) andcarbon dioxide production (CO₂) rates were measuredby electronically recording heart rate (HR) and physical activity (PA).Mean daily O₂ andCO₂ measurements by HR andPA were validated in adults (n = 10 women and 10 men) with room calorimeters. Thirteen linear and nonlinear functions of HR alone and HR combined with PA were tested as models of24-h O₂ andCO₂. Mean sleepO₂ andCO₂ were similar to basalmetabolic rates and were accurately estimated from HR alone[respective mean errors were 0.2 ± 0.8 (SD) and0.4 ± 0.6%]. The range of prediction errorsfor 24-h O₂ andCO₂ was smallestfor a model that used PA to assign HR for each minute to separateactive and inactive curves(O₂, 3.3 ± 3.5%; CO₂, 4.6 ± 3%). There were no significant correlations betweenO₂ orCO₂ errors and subject age,weight, fat mass, ratio of daily to basal energy expenditure rate, orfitness. O₂,CO₂, and energy expenditurerecorded for 3 free-living days were 5.6 ± 0.9 ml ^· min^{1 ·} kg¹,4.7 ± 0.8 ml ^· min^{1 ·} kg¹,and 7.8 ± 1.6 kJ/min, respectively. Combined HR and PA measured 24-h O₂ andCO₂ with a precisionsimilar to alternative methods.