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.

     

Airway thermal volume in humans and its relation to body size

Serikov, Vladimir B., E. Heidi Jerome, Neal W. Fleming,Peter G. Moore, Frederick A. Stawitcke, and Norman C. Staub.Airway thermal volume in humans and its relation to body size.J. Appl. Physiol. 83(2): 668-676, 1997.The objective of this study was to investigate the influence ofvolume ventilation(E) andcardiac output () on the temperature of the expiredgas at the distal end of the endotracheal tube in anesthetized humans.In 63 mechanically ventilated adults, we used a step decrease in thehumidity of inspired gas to cool the lungs. After change from humid todry gas ventilation, the temperature of the expired gas decreased. Weevaluated the relationship between the inverse monoexponential timeconstant of the temperature fall (1/) and eitherE or . WhenE wasincreased from 5.67 ± 1.28 to 7.14 ± 1.60 (SD) l/min(P = 0.02), 1/ did not changesignificantly [from 1.25 ± 0.38 to 1.21 ± 0.51 min¹,P = 0.81]. In the 11 patients in whom changed during the study period(from 5.07 ± 1.81 to 7.38 ± 2.45 l/min,P = 0.02), 1/ increasedcorrespondingly from 0.89 ± 0.22 to 1.52 ± 0.44 min¹(P = 0.003). We calculated the airwaythermal volume (ATV) as the ratio of the measured values to 1/ and related it to the body height (BH):ATV (liters) = 0.086 BH (cm)  9.55 (r = 0.90).

     

Ventilatory response to exercise in diabetic subjects with autonomic neuropathy

Tantucci, C., P. Bottini, M. L. Dottorini, E. Puxeddu, G. Casucci, L. Scionti, and C. A. Sorbini. Ventilatory response toexercise in diabetic subjects with autonomic neuropathy.J. Appl. Physiol. 81(5):1978-1986, 1996.We have used diabetic autonomic neuropathy as amodel of chronic pulmonary denervation to study the ventilatoryresponse to incremental exercise in 20 diabetic subjects, 10 with(Dan+) and 10 without (Dan) autonomic dysfunction, and in 10 normal control subjects. Although both Dan+ and Dan subjectsachieved lower O₂ consumption andCO₂ production(CO₂) thancontrol subjects at peak of exercise, they attained similar values ofeither minute ventilation(E) oradjusted ventilation (E/maximalvoluntary ventilation). The increment of respiratory rate withincreasing adjusted ventilation was much higher in Dan+ than inDan and control subjects (P < 0.05). The slope of the linearE/CO₂relationship was 0.032 ± 0.002, 0.027 ± 0.001 (P < 0.05), and 0.025 ± 0.001 (P < 0.001) ml/min inDan+, Dan, and control subjects, respectively. Bothneuromuscular and ventilatory outputs in relation to increasingCO₂ were progressivelyhigher in Dan+ than in Dan and control subjects. At peak ofexercise, end-tidal PCO₂ was muchlower in Dan+ (35.9 ± 1.6 Torr) than in Dan (42.1 ± 1.7 Torr; P < 0.02) and control (42.1 ± 0.9 Torr; P < 0.005) subjects.We conclude that pulmonary autonomic denervation affects ventilatoryresponse to stressful exercise by excessively increasing respiratoryrate and alveolar ventilation. Reduced neural inhibitory modulationfrom sympathetic pulmonary afferents and/or increasedchemosensitivity may be responsible for the higher inspiratoryoutput.

     

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.

     

Age-related declines in maximal aerobic capacity in regularly exercising vs. sedentary women: a meta-analysis

Fitzgerald, Margaret D., Hirofumi Tanaka, Zung V. Tran, andDouglas R. Seals. Age-related declines in maximal aerobic capacityin regularly exercising vs. sedentary women: a meta-analysis. J. Appl. Physiol. 83(1): 160-165, 1997.Our purpose was to determine the relationship between habitualaerobic exercise status and the rate of decline in maximal aerobiccapacity across the adult age range in women. A meta-analytic approachwas used in which mean maximal oxygen consumption(O_{2 max}) values fromfemale subject groups (ages 18-89 yr) were obtained from thepublished literature. A total of 239 subject groups from 109 studiesinvolving 4,884 subjects met the inclusion criteria and werearbitrarily separated into sedentary (groups = 107; subjects = 2,256),active (groups = 69; subjects = 1,717), and endurance-trained (groups = 63; subjects = 911) populations.O_{2 max} averaged 29.7 ± 7.8, 38.7 ± 9.2, and 52.0 ± 10.5 ml · kg¹ · min¹,respectively, and was inversely related to age within each population (r = 0.82 to 0.87, allP < 0.0001). The rate of decline inO_{2 max} withincreasing subject group age was lowest in sedentary women (3.5ml · kg¹ · min¹· decade¹), greater inactive women (4.4ml · kg¹ · min¹· decade¹), andgreatest in endurance-trained women (6.2ml · kg¹ · min¹ · decade¹)(all P < 0.001 vs. each other). Whenexpressed as percent decrease from mean levels at age ~25 yr, therates of decline inO_{2 max} were similarin the three populations (10.0 to 10.9%/decade). Therewas no obvious relationship between aerobic exercise status and therate of decline in maximal heart rate with age. The results of thiscross-sectional study support the hypothesis that, in contrast to theprevailing view, the rate of decline in maximal aerobic capacity withage is greater, not smaller, in endurance-trained vs. sedentary women.The greater rate of decline inO_{2 max} in endurance-trained populations may be related to their higher values asyoung adults (baseline effect) and/or to greater age-related reductions in exercise volume; however, it does not appear to berelated to a greater rate of decline in maximal heart rate with age.

     

Blood volume and cardiac index in rats after exchange transfusion with hemoglobin-based oxygen carriers

Migita, Russell, Armando Gonzales, Maria L. Gonzales, Kim D. Vandegriff, and Robert M. Winslow. Blood volume and cardiac indexin rats after exchange transfusion with hemoglobin-based oxygencarriers. J. Appl. Physiol. 82(6):1995-2002, 1997.We have measured plasma volume and cardiac indexin rats after 50% isovolemic exchange transfusion with humanhemoglobin cross-linked between the -chains withbis(3,5-dibromosalicyl)fumarate (Hb) and with bovine hemoglobinmodified with polyethylene glycol (PEGHb). Hb and PEGHb differ incolloid osmotic pressure (23.4 and 118.0 Torr, respectively), oxygenaffinity (oxygen half-saturation pressure of hemoglobin = 30.0 and 10.2 Torr, respectively), viscosity (1.00 and 3.39 cP, respectively), andmolecular weight (64,400 and 105,000, respectively). Plasma volume wasmeasured by Evans blue dye dilution modified for interference by plasmahemoglobin. Blood volumes in PEGHb-treated animals were significantlyelevated (74.0 ± 3.5 ml/kg) compared with animals treated withHb (49.0 ± 1.2 ml/kg) or Ringer lactate (48.0 ± 2.0 ml/kg) or with controls (58.2 ± 1.9 ml/kg). Heart rate reductionafter Hb exchange is opposite to that expected with blood volumecontraction, suggesting that Hb may have a direct myocardialdepressant action. The apparently slow elimination of PEGHb during the2 h after its injection is a consequence of plasma volume expansion:when absolute hemoglobin (concentration × plasma volume) iscompared for PEGHb and Hb, no difference in their eliminationrates is found. These studies emphasize the need to understand bloodvolume regulation when the effects of cell-free hemoglobin onhemodynamic measurements are evaluated.

     

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.

     

Chest wall mechanics in sustained microgravity

We assessed theeffects of sustained weightlessness on chest wall mechanics in fiveastronauts who were studied before, during, and after the 10-daySpacelab D-2 mission (n = 3)and the 180-day Euromir-95 mission (n = 2). We measured flow and pressure at the mouth and rib cage andabdominal volumes during resting breathing and during a relaxationmaneuver from midinspiratory capacity to functional residual capacity.Microgravity produced marked and consistent changes () in thecontribution of the abdomen to tidal volume [Vab/(Vab + Vrc), where Vab is abdominal volume and Vrc is rib cagevolume], which increased from 30.7 ± 3.5 (SE)% at1 G head-to-foot acceleration to 58.3 ± 5.7% at 0 G head-to-foot acceleration (P < 0.005). Values ofVab/(Vab + Vrc) did not change significantly during the 180 days of the Euromir mission, but in the two subjects Vab/(Vab + Vrc) was greater on postflight day1 than on subsequent postflight days or preflight. Inthe two subjects who produced satisfactory relaxation maneuvers, the slope of the Konno-Mead plot decreased in microgravity; this decrease was entirely accounted for by an increase in abdominal compliance because rib cage compliance did not change. These alterations aresimilar to those previously reported during short periods ofweightlessness inside aircrafts flying parabolic trajectories. They arealso qualitatively similar to those observed on going from upright tosupine posture; however, in contrast to microgravity, such posturalchange reduces rib cage compliance.

     

Peripheral O2 diffusion does not affect VO2 on-kinetics in isolated in situ canine muscle

To test thehypothesis that muscle O₂ uptake(O₂) on-kinetics islimited, at least in part, by peripheralO₂ diffusion, we determined theO₂ on-kinetics in1) normoxia (Control);2) hyperoxic gas breathing(Hyperoxia); and 3) hyperoxia andthe administration of a drug (RSR-13, Allos Therapeutics), whichright-shifts the Hb-O₂dissociation curve (Hyperoxia+RSR-13). The study was conducted inisolated canine gastrocnemius muscles(n = 5) during transitions from restto 3 min of electrically stimulated isometric tetanic contractions(200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% peakO₂). In all conditions,before and during contractions, muscle was pump perfused withconstantly elevated blood flow (), at a levelmeasured at steady state during contractions in preliminary trials withspontaneous . Adenosine was infusedintra-arterially to prevent inordinate pressure increases with theelevated . was measuredcontinuously, arterial and popliteal venousO₂ concentrations were determinedat rest and at 5- to 7-s intervals during contractions, andO₂ was calculated as · arteriovenous O₂ content difference.PO₂ at 50%HbO₂saturation (P₅₀) was calculated.Mean capillary PO₂(c_O2)was estimated by numerical integration.P₅₀ was higher in Hyperoxia+RSR-13[40 ± 1 (SE) Torr] than in Control and in Hyperoxia (31 ± 1 Torr). After 15 s of contractions,c_O2was higher in Hyperoxia (97 ± 9 Torr) vs. Control (53 ± 3 Torr) and in Hyperoxia+RSR-13 (197 ± 39 Torr) vs. Hyperoxia. Thetime to reach 63% of the difference between baseline and steady-stateO₂ during contractions was 24.7 ± 2.7 s in Control, 26.3 ± 0.8 s in Hyperoxia, and 24.7 ± 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement ofperipheral O₂ diffusion (obtainedby increasedc_O2at constant O₂ delivery) duringthe rest-to-contraction (60-70% of peakO₂) transition did notaffect muscle O₂on-kinetics.

     

Pulmonary blood flow redistribution by increased gravitational force

This study was undertaken to assess theinfluence of gravity on the distribution of pulmonary blood flow (PBF)using increased inertial force as a perturbation. PBF was studied inunanesthetized swine exposed toG_x (dorsal-to-ventraldirection, prone position), where G is the magnitude of the force ofgravity at the surface of the Earth, on the Armstrong LaboratoryCentrifuge at Brooks Air Force Base. PBF was measured using 15-µmfluorescent microspheres, a method with markedly enhanced spatialresolution. Each animal was exposed randomly to 1, 2, and3 G_x. Pulmonary vascularpressures, cardiac output, heart rate, arterial blood gases, and PBFdistribution were measured at each G level. Heterogeneity of PBFdistribution as measured by the coefficient of variation of PBFdistribution increased from 0.38 ± 0.05 to 0.55 ± 0.11 to0.72 ± 0.16 at 1, 2, and 3G_x, respectively. At 1G_x, PBF was greatest in theventral and cranial and lowest in the dorsal and caudal regions of thelung. With increased G_x,this gradient was augmented in both directions. Extrapolation of thesevalues to 0 G predicts a slight dorsal (nondependent) region dominanceof PBF and a coefficient of variation of 0.22 in microgravity. Analysisof variance revealed that a fixed component (vascular structure)accounted for 81% and nonstructure components (including gravity)accounted for the remaining 19% of the PBF variance across the entireexperiment (all 3 gravitational levels). The results are inconsistentwith the predictions of the zone model.

     

Reductions in visceral fat during weight loss and walking are associated with improvements in {V}O2 max

The accumulation ofvisceral fat is independently associated with an increased risk forcardiovascular disease. The aim of this study was to determine whetherthe loss of visceral adipose tissue area (VAT; computed tomography) isrelated to improvements in maximal O₂ uptake(O_2 max) during a weight loss(250-350 kcal/day deficit) and walking (3 days/wk, 30-40 min)intervention. Forty obese [body fat 47 ± 1 (SE) %], sedentary(O_2 max 19 ± 1 ml · kg¹ · min¹)postmenopausal women (age 62 ± 1 yr) participated in the study. The intervention resulted in significant declines in body weight (8%), total fat mass (dual-energy X-ray absorptiometry; 17%), VAT(17%), and subcutaneous adipose tissue area (17%) with no changein lean body mass (all P < 0.001). Women with anaverage 10% increase in O_2 max reducedVAT by an average of 20%, whereas those who did not increaseO_2 max decreased VAT by only 10%,despite comparable reductions in body fat, fat mass, and subcutaneousadipose tissue area. The decrease in VAT was independently related tothe change in O_2 max(r² = 0.22; P < 0.01) andfat mass (r² = 0.08; P = 0.05). These data indicate that greater improvements inO_2 max with weight loss and walking areassociated with greater reductions in visceral adiposity in obesepostmenopausal women.

     

Greater rate of decline in maximal aerobic capacity with age in physically active vs. sedentary healthy women

Tanaka, Hirofumi, Christopher A. DeSouza, Pamela P. Jones,Edith T. Stevenson, Kevin P. Davy, and Douglas R. Seals. Greater rate of decline in maximal aerobic capacity with age in physically active vs. sedentary healthy women. J. Appl.Physiol. 83(6): 1947-1953, 1997.Using ameta-analytic approach, we recently reported that the rate of declinein maximal oxygen uptake(O_{2 max}) with age inhealthy women is greatest in the most physically active and smallest inthe least active when expressed in milliliters per kilogram per minuteper decade. We tested this hypothesis prospectively underwell-controlled laboratory conditions by studying 156 healthy, nonobesewomen (age 20-75 yr): 84 endurance-trained runners (ET) and 72 sedentary subjects (S). ET were matched across the age range forage-adjusted 10-km running performance. Body mass was positivelyrelated with age in S but not in ET. Fat-free mass was not differentwith age in ET or S. Maximal respiratory exchange ratio and rating ofperceived exertion were similar across age in ET and S, suggestingequivalent voluntary maximal efforts. There was a significant butmodest decline in running mileage, frequency, and speed with advancingage in ET.O_{2 max}(ml · kg¹ · min¹)was inversely related to age (P < 0.001) in ET (r = 0.82) and S(r = 0.71) and was higher atany age in ET. Consistent with our meta-analysic findings,the absolute rate of decline inO_{2 max} was greater inET (5.7ml · kg¹ · min¹ · decade¹)compared with S (3.2 ml · kg¹ · min¹ · decade¹;P < 0.01), but the relative (%)rate of decline was similar (9.7 vs 9.1%/decade; notsignificant). The greater absolute rate of decline inO_{2 max} in ET comparedwith S was not associated with a greater rate of decline in maximalheart rate (5.6 vs. 6.2beats · min¹ · decade¹),nor was it related to training factors. The present cross-sectional findings provide additional evidence that the absolute, but not therelative, rate of decline in maximal aerobic capacity with age may begreater in highly physically active women compared with theirsedentary healthy peers. This difference does not appear to be relatedto age-associated changes in maximal heart rate, bodycomposition, or training factors.

     

Effects of dopamine and domperidone on ventilatory sensitivity to hypoxia after 8h of isocapnic hypoxia

Acclimatization to altitude involves an increase in the acutehypoxic ventilatory response (AHVR). Because low-dose dopamine decreases AHVR and domperidone increases AHVR, the increase in AHVR ataltitude may be generated by a decrease in peripheral dopaminergicactivity. The AHVR of nine subjects was determined with and without aprior period of 8 h of isocapnic hypoxia under each of threepharmacological conditions: 1)control, with no drug administered;2) dopamine (3 µg · min¹ · kg¹);and 3) domperidone (Motilin, 40 mg).AHVR increased after hypoxia (P  0.001). Dopaminedecreased (P  0.01), and domperidone increased (P  0.005) AHVR. The effect of both drugs on AHVR appearedlarger after hypoxia, an observation supported by a significantinteraction between prior hypoxia and drug in the analysis of variance(P  0.05). Although the increasedeffect of domperidone after hypoxia of 0.40 l · min¹ · %saturation¹[95% confidence interval (CI) 0.11 to 0.92 l · min¹ · %¹]did not reach significance, the lower limit for this confidence interval suggests that little of the increase in AHVR after sustained hypoxia was brought about by a decrease in peripheral dopaminergic inhibition.

     

Mechanical and metabolic determination of VO2 and fatigue during repetitive isometric contractions in situ

Repetitiveisometric tetanic contractions (1/s) of the caninegastrocnemius-plantaris muscle were studied either at optimal length(L_o) or shortlength (L_s;~0.9 · L_o),to determine the effects of initial length on mechanical and metabolicperformance in situ. Respective averages of mechanical and metabolicvariables were(L_o vs.L_s, allP < 0.05) passive tension (preload) = 55 vs. 6 g/g, maximal active tetanic tension(P_o) = 544 vs. 174 (0.38 · P_o)g/g, maximal blood flow () = 2.0 vs. 1.4 ml · min¹ · g¹,and maximal oxygen uptake(O₂) = 12 vs. 9 µmol · min¹ · g¹.Tension at L_odecreased to0.64 · P_o over20 min of repetitive contractions, demonstrating fatigue; there were nosignificant changes in tension atL_s. In separatemuscles contracting atL_o, was set to that measured atL_s (1.1 ml · min¹ · g¹),resulting in decreased O₂(7 µmol · min¹ · g¹),and rapid fatigue, to0.44 · P_o. Thesedata demonstrate that 1)muscles at L_ohave higher andO₂ values than those at L_s;2) fatigue occurs atL_o with highO₂, adjusting metabolic demand (tension output) to match supply; and3) the lack of fatigue atL_s with lowertension, , andO₂ suggestsadequate matching of metabolic demand, set low by shortmuscle length, with supply optimized by low preload. Thesedifferences in tension andO₂ betweenL_o andL_s groupsindicate that muscles contracting isometrically at initial lengthsshorter than L_oare working under submaximal conditions.

     

Oxygen transport in conscious newborn dogs during hypoxic hypometabolism

We questioned whether the decrease inO₂ consumption(O₂) during hypoxia innewborns is a regulated response or reflects a limitation inO₂ availability. Experiments wereconducted on previously instrumented conscious newborn dogs.O₂ was measured at a warmambient temperature (30°C, n = 7)or in the cold (20°C, n = 6),while the animals breathed air or were sequentially exposed to 15 minof fractional inspired O₂(FI_O2): 21, 18, 15, 12, 10, 8, and 6%. In normoxia,O₂ averaged 15 ± 1 (SE)and 25 ± 1 ml · kg¹ · min¹in warm and cold conditions, respectively. In the warmcondition, hypometabolism (i.e., hypoxicO₂ < normoxicO₂) occurred at FI_O2 10%, whereas in thecold condition, hypometabolism occurred atFI_O2 12%. The sameresults were obtained in a separate group(n = 14) of noninstrumented puppies.For all levels of FI_O2 withhypometabolism, the relationships between measures ofO₂ availability (arterialO₂ saturation or content, venousPO₂ or saturation,x-axis) vs.O₂(y-axis) had lower slopes in warm than in coldconditions. Hence, O₂ during hypometabolism in the warm condition was not the maximal attainable for the level of oxygenation. The results do not support thepossibility that the hypoxic drop inO₂ in the newborn reflects a limitation in O₂availability. The results are compatible with the ideathat the phenomenon is one of "regulated conformism" tohypoxia.

     

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.

     

Respiratory muscle work compromises leg blood flow during maximal exercise

Harms, Craig A., Mark A. Babcock, Steven R. McClaran, DavidF. Pegelow, Glenn A. Nickele, William B. Nelson, and Jerome A. Dempsey.Respiratory muscle work compromises leg blood flow during maximalexercise. J. Appl. Physiol.82(5): 1573-1583, 1997.We hypothesized that duringexercise at maximal O₂ consumption (O_{2 max}),high demand for respiratory muscle blood flow() would elicit locomotor muscle vasoconstrictionand compromise limb . Seven male cyclists(O_{2 max} 64 ± 6 ml · kg¹ · min¹)each completed 14 exercise bouts of 2.5-min duration atO_{2 max} on a cycleergometer during two testing sessions. Inspiratory muscle work waseither 1) reduced via aproportional-assist ventilator, 2)increased via graded resistive loads, or3) was not manipulated (control).Arterial (brachial) and venous (femoral) blood samples, arterial bloodpressure, leg (legs;thermodilution), esophageal pressure, andO₂ consumption(O₂) weremeasured. Within each subject and across all subjects, at constantmaximal work rate, significant correlations existed(r = 0.74-0.90;P < 0.05) between work of breathing(Wb) and legs (inverse), leg vascular resistance (LVR), and leg O₂(O_{2 legs};inverse), and between LVR and norepinephrine spillover. Mean arterialpressure did not change with changes in Wb nor did tidal volume orminute ventilation. For a ±50% change from control in Wb,legs changed 2 l/min or 11% of control, LVRchanged 13% of control, and O₂extraction did not change; thusO_{2 legs}changed 0.4 l/min or 10% of control. TotalO_{2 max} was unchangedwith loading but fell 9.3% with unloading; thusO_{2 legs}as a percentage of totalO_{2 max} was 81% incontrol, increased to 89% with respiratory muscle unloading, anddecreased to 71% with respiratory muscle loading. We conclude that Wbnormally incurred during maximal exercise causes vasoconstriction inlocomotor muscles and compromises locomotor muscle perfusion andO₂.

     

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.

     

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.

     

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.