Importance of the lactate anion in control of breathing

Hardarson, Thorir, Jon O. Skarphedinsson, and TorarinnSveinsson. Importance of the lactate anion in control ofbreathing. J. Appl. Physiol. 84(2):411-416, 1998.The purpose of this study was to examine theeffects of raising the arterialLa andK⁺ levels on minute ventilation(E) in rats. EitherLa or KCl solutions wereinfused in anesthetized spontaneously breathing Wistar rats to raisethe respective ion arterial concentration ([La] and[K⁺]) gradually tolevels similar to those observed during strenuous exercise.E, blood pressure, and heart rate wererecorded continuously, and arterial[La],[K⁺], pH, and bloodgases were repeatedly measured from blood samples. To prevent changesin pH during the Lainfusions, a solution of sodium lactate and lactic acid was used. Raising [La] to13.2 ± 0.6 (SE) mM induced a 47.0 ± 4.0% increase inE without any concomitant changes ineither pH or PCO₂. Raising[K⁺] to 7.8 ± 0.11 mM resulted in a 20.3 ± 5.28% increase inE without changes in pH. Thus ourresults show that Laitself, apart from lactic acidosis, may be important in increasing E during strenuous exercise, and weconfirm earlier results regarding the role of arterial[K⁺] in the control ofE during exercise.

     

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.

     

Role for anions in pulmonary endothelial permeability

Griffin, M. Pamela. Role for anions in pulmonaryendothelial permeability. J. Appl.Physiol. 83(2): 615-622, 1997.-Adrenergic stimulation reduces albumin permeation across pulmonary artery endothelial monolayers and induces changes in cell morphology that aremediated by Cl flux. Wetested the hypothesis that anion-mediated changes in endothelial cellsresult in changes in endothelial permeability. We measured permeationof radiolabeled albumin across bovine pulmonary arterial endothelialmonolayers when the extracellular anion was Cl,Br,I,F, acetate(Ac), gluconate(G), and propionate(Pr). Permeability toalbumin (P_albumin)was calculated before and after addition of 0.2 mM of thephosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), whichreduces permeability. InCl, theP_albumin was 3.05 ± 0.86 × 10⁶ cm/s andfell by 70% with the addition of IBMX. The initialP_albumin was lowest forPr andAc. InitialP_albumin was higher inBr,I,G, andF than inCl. A permeability ratiowas calculated to examine the IBMX effect. The greatest IBMX effect wasseen when Cl was theextracellular anion, and the order among halide anions wasCl > Br > I > F. Although the level ofextracellular Ca²⁺ concentration([Ca²⁺]_o)varied over a wide range in the anion solutions,[Ca²⁺]_odid not systematically affect endothelial permeability in this system.When Cl was theextracellular anion, varying[Ca²⁺]_ofrom 0.2 to 2.8 mM caused a change in initialP_albumin but no changein the IBMX effect. The anion channel blockers4-acetamido-4-isothiocyanotostilbene-2,2-disulfonic acid(0.25 mM) and anthracene-9-carboxylic acid (0.5 mM) significantly altered initialP_albumin and the IBMXeffect. The anion transport blockers bumetanide (0.2 mM) and furosemide(1 mM) had no such effects. We conclude that extracellular anionsinfluence bovine pulmonary arterial endothelial permeability and thatthe pharmacological profile fits better with the activity of anionchannels than with other anion transport processes.

     

Kinetics of oxygen uptake at the onset of exercise in boys and men

The objective of this study was to compare theO₂ uptake(O₂) kinetics at the onsetof heavy exercise in boys and men. Nine boys, aged 9-12 yr, and 8 men, aged 19-27 yr, performed a continuous incremental cyclingtask to determine peak O₂(O_{2 peak}).On 2 other days, subjects performed each day four cycling tasks at 80 rpm, each consisting of 2 min of unloaded cycling followed twice bycycling at 50%O_{2 peak} for 3.5 min,once by cycling at 100%O_{2 peak} for 2 min,and once by cycling at 130%O_{2 peak} for 75 s.O₂ deficit was not significantlydifferent between boys and men (respectively, 50%O_{2 peak} task: 6.6 ± 11.1 vs. 5.5 ± 7.3 ml · min¹ · kg¹;100% O_{2 peak} task:28.5 ± 8.1 vs. 31.8 ± 6.3 ml · min¹ · kg¹;and 130%O_{2 peak}task: 30.1 ± 5.7 vs. 35.8 ± 5.3 ml · min¹ · kg¹).To assess the kinetics, phase I was excluded from analysis. Phase IIO₂ kinetics could bedescribed in all cases by a monoexponential function. ANOVA revealed nodifferences in time constants between boys and men (respectively, 50%O_{2 peak}task: 22.8 ± 5.1 vs. 26.4 ± 4.1 s; 100%O_{2 peak} task: 28.0 ± 6.0 vs. 28.1 ± 4.4 s; and 130%O_{2 peak} task: 19.8 ± 4.1 vs. 20.7 ± 5.7 s). In conclusion, O₂ deficit and fast-componentO₂ on-transientsare similar in boys and men, even at high exercise intensities, whichis in contrast to the findings of other studies employing simplermethods of analysis. The previous interpretation that children relyless on nonoxidative energy pathways at the onset of heavy exercise isnot supported by our findings.

     

Contributions of pulmonary perfusion and ventilation to heterogeneity in VA/Q measured by PET

Treppo, Steven, Srboljub M. Mijailovich, and José G. Venegas. Contributions of pulmonary perfusion and ventilation toheterogeneity in A/measured by PET. J. Appl. Physiol. 82(4): 1163-1176, 1997. To estimate the contributions of the heterogeneity in regionalperfusion () and alveolar ventilation(A) to that of ventilation-perfusionratio (A/), we haverefined positron emission tomography (PET) techniques to image localdistributions of andA per unit of gas volume content(s and sA,respectively) and VA/ indogs. sA was assessed in two ways:1) the washout of ¹³NN tracer after equilibrationby rebreathing (sA_i), and2) the ratio of an apneic image after a bolus intravenousinfusion of ¹³NN-saline solution to an image collectedduring a steady-state intravenous infusion of the same solution(sA_p).sA_p was systematically higher than sA_i in allanimals, and there was a high spatial correlation betweens andsA_p in both body positions(mean correlation was 0.69 prone and 0.81 supine) suggesting thatventilation to well-perfused units was higher than to those poorlyperfused. In the prone position, the spatial distributions ofs, sA_p, and A/ were fairlyuniform with no significant gravitational gradients; however, in thesupine position, these variables were significantly more heterogeneous,mostly because of significant gravitational gradients (15, 5.5, and10%/cm, respectively) accounting for 73, 33, and 66% of thecorresponding coefficient of variation (CV)² values. Weconclude that, in the prone position, gravitational forces in blood andlung tissues are largely balanced out by dorsoventral differences inlung structure. In the supine position, effects of gravity andstructure become additive, resulting in substantial gravitationalgradients in s andsA_p, with the higherheterogeneity inA/ caused by agravitational gradient in s, only partially compensated by that in sA.

     

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.

     

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.

     

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.

     

Effects of hyperthermia on contraction and dilatation of rabbit femoral arteries

To analyze the effect of hyperthermia on thevascular response, the isometric response of isolated rabbit femoralartery segments was recorded at 37°C and hyperthermia (41 and44°C). Contraction to potassium (5 × 10³-5 × 10² M) was significantlygreater at 41 and 44 than at 37°C and increased by inhibition ofnitric oxide (NO) synthesis withN-nitro-L-arginine(L-NNA;10⁴ M) or endotheliumremoval at 37°C but not at 41 or 44°C. Norepinephrine (10⁹-10⁴M) produced a concentration-dependent contraction greater at 41 or 44 than at 37°C and not modified by endothelium removal orL-NNA at either temperature.Phenylephrine(10⁹-10⁴M) produced a contraction increased by warming to 44°C but not to41°C. The specific₂-adrenoceptor agonist BHT-920produced a weak contraction, reduced by the₁-adrenoceptor antagonist prazosin (10⁶ M) andincreased at 44°C but not at 41°C. The concentration-dependent contraction to endothelin-1 (ET-1;10¹¹-10⁷M) was increased by warming to 41 and 44°C and by endothelium removal or L-NNA at 37°C butnot at 41 or 44°C. Response to ET-1 was reduced by endothelinET_A-receptor antagonist BQ-123(10⁵ M) andET_B-receptor antagonist BQ-788(10⁵ M). In arteriesprecontracted with ET-1(10⁸-3 × 10⁸ M), relaxation tosodium nitroprusside(10⁸-10⁴M) was increased at 41 and 44°C vs. at 37°C, but that of ACh (10⁸-10⁴M) or adenosine(10⁸-10⁴M) was not different at all temperatures studied. Relaxation to ACh,but not adenosine, was reduced similarly byL-NNA at all temperaturesstudied. These results suggest hyperthermia in muscular arteries mayinhibit production of, and increase dilatation to, NO, resulting inunchanged relaxation to ACh and increased constriction to KCl and ET-1,and may increase constriction to stimulation of₁-adrenoceptors byNO-independent mechanisms.

     

Nitric oxide and beta -adrenergic agonist-induced bronchial arterial vasodilation

Charan, Nirmal B., Shane R. Johnson, S. Lakshminarayan,William H. Thompson, and Paula Carvalho. Nitric oxide and-adrenergic agonist-induced bronchial arterial vasodilation.J. Appl. Physiol. 82(2): 686-692, 1997.In anesthetized sheep, we measured bronchial blood flow(br) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) givenfor 5 min and 5 ml of aerosolized isoetharine (1.49 × 10² M concentration).NO and isoetharine increased br from 26.5 ± 6.5 to 39.1 (SE) ± 10.6 and 39.7 ± 10.7 ml/min,respectively (n = 5).Administration of NO immediately after isoetharine further increasedbr to 57.3 ± 15.1 ml/min. NO synthase inhibitorN-nitro-L-arginine methyl esterhydrochloride (L-NAME; 30 mg/kg, in 20 ml salinegiven iv) decreased br to 14.6 ± 2.6 ml/min. NO given three times alternately with isoetharine progressively increased br from 14.6 ± 2.6 to 74.3 ± 17.0 ml/min, suggesting that NO and isoetharine potentiatevasodilator effects of each other. In three other sheep, afterL-NAME, three sequential doses of isoetharine increased br from 10.2 ± 3.4 to11.5 ± 5.7, 11.7 ± 4.7, and 13.3 ± 5.7 ml/min,respectively, indicating that effects of isoetharine are predominantlymediated through synthesis of NO. When this was followed by threesequential administrations of NO, br increased by146, 172, and 185%, respectively. Thus in the bronchial circulationthere seems to be a close interaction between adenosine3,5-cyclic monophosphate- and guanosine3,5-cyclic monophosphate-mediated vasodilatation.

     

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).

     

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.

     

Smaller lungs in women affect exercise hyperpnea

We subjected 29 healthy young women (age: 27 ± 1 yr) with a wide range of fitness levels [maximal oxygenuptake (O_{2 max}): 57 ± 6 ml · kg¹ · min¹;35-70ml · kg¹ · min¹]to a progressive treadmill running test. Our subjects had significantly smaller lung volumes and lower maximal expiratory flow rates, irrespective of fitness level, compared with predicted values for age-and height-matched men. The higher maximal workload in highly fit(O_{2 max} > 57 ml · kg¹ · min¹,n = 14) vs. less-fit(O_{2 max} < 56 ml · kg¹ · min¹,n = 15) women caused a higher maximalventilation (E) with increased tidal volume (VT)and breathing frequency (f_b) atcomparable maximal VT/vitalcapacity (VC). More expiratory flow limitation (EFL; 22 ± 4% ofVT) was also observed duringheavy exercise in highly fit vs. less-fit women, causing higherend-expiratory and end-inspiratory lung volumes and greater usage oftheir maximum available ventilatory reserves.HeO₂ (79% He-21%O₂) vs. room air exercise trialswere compared (with screens added to equalize external apparatusresistance). HeO₂ increasedmaximal expiratory flow rates (20-38%) throughout the range ofVC, which significantly reduced EFL during heavy exercise. When EFL wasreduced with HeO₂, VT,f_b, andE (+16 ± 2 l/min) weresignificantly increased during maximal exercise. However, in theabsence of EFL (during room air exercise),HeO₂ had no effect onE. We conclude that smaller lungvolumes and maximal flow rates for women in general, and especiallyhighly fit women, caused increased prevalence of EFL during heavyexercise, a relative hyperinflation, an increased reliance onf_b, and a greater encroachment onthe ventilatory "reserve." Consequently,VT andE are mechanically constrained duringmaximal exercise in many fit women because the demand for highexpiratory flow rates encroaches on the airways' maximum flow-volumeenvelope.

     

Association of chest wall motion and tidal volume responses during CO2 rebreathing

Yan, Sheng, Pawel Sliwinski, and Peter T. Macklem.Association of chest wall motion and tidal volume responses during CO₂ rebreathing.J. Appl. Physiol. 81(4):1528-1534, 1996.The purpose of this study is to investigate theeffect of chest wall configuration at end expiration on tidal volume(VT) response duringCO₂ rebreathing. In a group of 11 healthy male subjects, the changes in end-expiratory andend-inspiratory volume of the rib cage (Vrc,E andVrc,I, respectively) and abdomen (Vab,E and Vab,I, respectively) measured by linearizedmagnetometers were expressed as a function of end-tidalPCO₂(PET_CO2). The changes inend-expiratory and end-inspiratory volumes of the chest wall(Vcw,E and Vcw,I,respectively) were calculated as the sum of the respectiverib cage and abdominal volumes. The magnetometer coils were placed atthe level of the nipples and 1-2 cm above the umbilicus andcalibrated during quiet breathing against theVT measured from apneumotachograph. TheVrc,E/PET_CO2 slope was quite variable among subjects. It was significantly positive (P < 0.05) in fivesubjects, significantly negative in four subjects(P < 0.05), and not different fromzero in the remaining two subjects. TheVab,E/PET_CO2slope was significantly negative in all subjects(P < 0.05) with a much smallerintersubject variation, probably suggesting a relatively more uniformrecruitment of abdominal expiratory muscles and a variable recruitmentof rib cage muscles during CO₂rebreathing in different subjects. As a group, the meanVrc,E/PET_CO2,Vab,E/PET_CO2, andVcw,E/PET_CO2slopes were 0.010 ± 0.034, 0.030 ± 0.007, and0.020 ± 0.032 l / Torr, respectively;only theVab,E/PET_CO2 slope was significantly different from zero. More interestingly, theindividualVT/PET_CO2slope was negatively associated with theVrc,E/PET_CO2(r = 0.68,P = 0.021) and Vcw,E/PET_CO2slopes (r = 0.63,P = 0.037) but was not associated withtheVab,E/PET_CO2slope (r = 0.40, P = 0.223). There was no correlation oftheVrc,E/PET_CO2 andVcw,E/PET_CO2slopes with age, body size, forced expiratory volume in 1 s, orexpiratory time. The groupVab,I/PET_CO2 slope (0.004 ± 0.014 l / Torr) was not significantlydifferent from zero despite theVT nearly being tripled at theend of CO₂ rebreathing. Inconclusion, the individual VTresponse to CO₂, althoughindependent of Vab,E, is a function ofVrc,E to the extent that as theVrc,E/PET_CO2slope increases (more positive) among subjects, theVT response toCO₂ decreases. These results maybe explained on the basis of the respiratory muscle actions andinteractions on the rib cage.

     

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.

     

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.

     

Adrenergic beta 1- and beta 1+2-receptor blockade suppress the natural killer cell response to head-up tilt in humans

Klokker, M., N. H. Secher, P. Madsen, M. Pedersen, and B. K. Pedersen. Adrenergic ₁-and ₁₊₂-receptor blockade suppress the natural killer cell response to head-up tilt in humans. J. Appl. Physiol. 83(5):1492-1498, 1997.To evaluate stress-induced changes in bloodleukocytes with emphasis on the natural killer (NK) cells, eight malevolunteers were followed during three trials of head-up tilt withadrenergic ₁- (metoprolol) and₁₊₂- (propranolol) blockade andwith saline (control) infusions. The ₁- and₁₊₂-receptor blockade did notaffect the appearance of presyncopal symptoms, but the head-up tiltinduced a transient lymphocytosis that was abolished by₁₊₂-receptor blockade but notby ₁-receptor blockade. Head-uptilt also resulted in delayed neutrophilia, which was insensitive to-receptor blockade. Lymphocyte subset analysis revealed that thehead-up tilt resulted in a twofold increase in the percentage andabsolute number of CD3/CD16⁺andCD3/CD56⁺NK cells in peripheral blood and that this increase was partially blocked by metoprolol and abolished by propranolol. The NKcell activity on a per NK cell basis did not change during head-up tilt, indicating that the cytotoxic capability of NK cells recruited tocirculation is unchanged. The data suggest that the head-up tilt-induced lymphocytosis was due mainly toCD16⁺ andCD56⁺ NK cells and that theirrecruitment to the blood was inhibited by₁- and especially₁₊₂-receptor blockade. Thusstress-induced recruitment of lymphocytes, and of NK cells inparticular, is mediated by epinephrine through activation of-receptors on the lymphocytes.

     

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.

     

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.

     

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.