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.

     

Mitochondrial redox state as a potential detector of liver dysoxia in vivo

Dysoxia canbe defined as ATP flux decreasing in proportion toO₂ availability with preserved ATPdemand. Hepatic venous -hydroxybutyrate-to-acetoacetate ratio(-OHB/AcAc) estimates liver mitochondrial NADH/NAD and may detectthe onset of dysoxia. During partial dysoxia (as opposed to anoxia),however, flow may be adequate in some liver regions, diluting effluentfrom dysoxic regions, thereby rendering venous -OHB/AcAc unreliable.To address this concern, we estimated tissue ATP whilegradually reducing liver blood flow of swine to zero in a nuclearmagnetic resonance spectrometer. ATP flux decreasing withO₂ availability was taken asO₂ uptake(O₂) decreasing inproportion to O₂ delivery(O₂);and preserved ATP demand was taken as increasingP_i/ATP.O₂, tissueP_i/ATP, and venous -OHB/AcAcwere plotted againstO₂to identify critical inflection points. Tissue dysoxia required meanO₂for the group to be critical for bothO₂ and forP_i/ATP. CriticalO₂values for O₂ andP_i/ATP of 4.07 ± 1.07 and 2.39 ± 1.18 (SE) ml · 100 g¹ · min¹,respectively, were not statistically significantly different but notclearly the same, suggesting the possibility that dysoxia might havecommenced after O₂ begandecreasing, i.e., that there could have been"O₂ conformity." CriticalO₂for venous -OHB/AcAc was 2.44 ± 0.46 ml · 100 g¹ · min¹(P = NS), nearly the same as that forP_i/ATP, supporting venous -OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector ofdysoxia in liver.

     

Influence of age and gender on cardiac output-VO2 relationships during submaximal cycle ergometry

Proctor, David N., Kenneth C. Beck, Peter H. Shen, Tamara J. Eickhoff, John R. Halliwill, and Michael J. Joyner. Influence ofage and gender on cardiacoutput-O₂ relationshipsduring submaximal cycle ergometry. J. Appl.Physiol. 84(2): 599-605, 1998.It is presentlyunclear how gender, aging, and physical activity status interact todetermine the magnitude of the rise in cardiac output(c) during dynamic exercise. To clarify this issue,the present study examined thec-O₂ uptake(O₂) relationship duringgraded leg cycle ergometry in 30 chronically endurance-trained subjects from four groups (n = 6-8/group): younger men (20-30 yr), older men (56-72yr), younger women (24-31 yr), and older women(51-72 yr). c (acetylene rebreathing), strokevolume (c/heart rate), and whole bodyO₂ were measured at restand during submaximal exercise intensities (40, 70, and ~90% of peakO₂). Baseline restinglevels of c were 0.6-1.2 l/min less in theolder groups. However, the slopes of thec-O₂relationship across submaximal levels of cycling were similar among allfour groups (5.4-5.9 l/l). The absolute cassociated with a given O₂(1.0-2.0 l/min) was also similar among groups. Resting andexercise stroke volumes (ml/beat) were lower in women than in men butdid not differ among age groups. However, older men and women showed areduced ability, relative to their younger counterparts, to maintainstroke volume at exercise intensities above 70% of peakO₂. This latter effect wasmost prominent in the oldest women. These findings suggest that neitherage nor gender has a significant impact on thec-O₂ relationships during submaximal cycle ergometry among chronically endurance-trained individuals.

     

Faster adjustment of O2 delivery does not affect VO2 on-kinetics in isolated in situ canine muscle

The mechanism(s)limiting muscle O₂ uptake(O₂) kinetics wasinvestigated in isolated canine gastrocnemius muscles(n = 7) during transitions from restto 3 min of electrically stimulated isometric tetanic contractions(200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% of peakO₂). Two conditions weremainly compared: 1) spontaneousadjustment of blood flow () [control, spontaneous (C Spont)]; and2) pump-perfused, adjusted ~15 s before contractions at aconstant level corresponding to the steady-state value duringcontractions in C Spont [faster adjustment ofO₂ delivery (FastO₂ Delivery)]. During FastO₂ Delivery, 1-2 ml/min of10² M adenosine wereinfused intra-arterially to prevent inordinate pressure increases withthe elevated . The purpose of the study was todetermine whether a faster adjustment ofO₂ delivery would affectO₂ kinetics. was measured continuously; arterial(Ca_O2) and popliteal venous(Cv_O2)O₂ contents were determined atrest and at 5- to 7-s intervals during contractions;O₂ delivery was calculated as · Ca_O2,and O₂ was calculated as · arteriovenous O₂ content difference. Times toreach 63% of the difference between baseline and steady-stateO₂ during contractions were23.8 ± 2.0 (SE) s in C Spont and 21.8 ± 0.9 s in FastO₂ Delivery (not significant). Inthe present experimental model, elimination of any delay inO₂ delivery during therest-to-contraction transition did not affect muscleO₂ kinetics, which suggeststhat this kinetics was mainly set by an intrinsic inertia of oxidativemetabolism.

     

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.

     

Effect of prolonged heavy exercise on pulmonary gas exchange in horses

During short-term maximal exercise,horses have impaired pulmonary gas exchange, manifested by diffusionlimitation and arterial hypoxemia, without marked ventilation-perfusion(A/)inequality. Whether gas exchange deteriorates progressively duringprolonged submaximal exercise has not been investigated. Sixthoroughbred horses performed treadmill exercise at ~60% of maximaloxygen uptake until exhaustion (28-39 min). Multipleinert gas, blood-gas, hemodynamic, metabolic rate, and ventilatory datawere obtained at rest and 5-min intervals during exercise. Oxygenuptake, cardiac output, and alveolar-arterialPO₂ gradient were unchanged after thefirst 5 min of exercise. Alveolar ventilation increased progressivelyduring exercise, from increased tidal volume and respiratory frequency,resulting in an increase in arterialPO₂ and decrease in arterialPCO₂. At rest there was minimal A/inequality, log SD of the perfusion distribution (logSD) = 0.20. This doubled by 5 min of exercise (logSD = 0.40) butdid not increase further. There was no evidence of alveolar-end-capillary diffusion limitation during exercise. However, there was evidence for gas-phase diffusion limitation at all time points, and enflurane was preferentially overretained. Horses maintainexcellent pulmonary gas exchange during exhaustive, submaximal exercise. AlthoughA/inequality is greater than at rest, it is less than observed in mostmammals and the effect on gas exchange is minimal.

     

Ventilation-perfusion alterations after smoke inhalation injury in an ovine model

Shimazu, Takeshi, Tetsuo Yukioka, Hisashi Ikeuchi, Arthur D. Mason, Jr., Peter D. Wagner, and Basil A. Pruitt, Jr.Ventilation-perfusion alterations after smoke inhalation injury inan ovine model. J. Appl. Physiol.81(5): 2250-2259, 1996.To study the pathophysiological mechanismof progressive hypoxemia after smoke inhalation injury, alterations inventilation-perfusion ratio(A/)were studied in an ovine model by using the multiple inert gaselimination technique. Because ethane was detected in expired gas ofsome sheep, we replaced ethane with krypton, which was a uniqueapplication of the multiple inert gas elimination technique when one ofthe experimental gases is present in the inspirate. Severity-related changes were studied 24 h after injury in control and mild, moderate, and severe inhalation injury groups. Time-related changes were studiedin controls and sheep with moderate injury at 6, 12, 24, and 72 h.Arterial PO₂ decreased progressivelywith severity of injury as well as with time. In smoke-exposed animals,blood flow was recruited to lowA/compartment (0 < A/ < 0.1; 17.6 ± 10.6% of cardiac output, 24 h,moderate injury) from normal A/compartment (0.1 < A/ < 10). However, increases in true shunt(A/ = 0; 5.6 ± 2.5%, 24 h, moderate injury) and dead space were notconsistent findings. TheA/patterns suggest the primary change in smoke inhalation injury to be adisturbance of ventilation.

     

Increasing maximal heart rate increases maximal O2 uptake in rats acclimatized to simulated altitude

Gonzalez, Norberto C., Richard L. Clancy, Yoshihiro Moue,and Jean-Paul Richalet. Increasing maximal heart rate increases maximal O₂ uptake in ratsacclimatized to simulated altitude. J. Appl.Physiol. 84(1): 164-168, 1998.Maximal exerciseheart rate (HR_max) is reducedafter acclimatization to hypobaric hypoxia. The lowHR_max contributes to reducemaximal cardiac output(_max) andmay limit maximal O₂ uptake(O_{2 max}). Theobjective of these experiments was to test the hypothesisthat the reduction in_max afteracclimatization to hypoxia, due, in part, to the lowHR_max, limitsO_{2 max}. Ifthis hypothesis is correct, an increase in _max wouldresult in a proportionate increase inO_{2 max}. Rats acclimatized to hypobaric hypoxia [inspiredPO₂(PI_O2) = 69.8 ± 3 Torr for 3 wk] exercised on a treadmill in hypoxic (PI_O2 = 71.7 ± 1.1 Torr) or normoxic conditions(PI_O2 = 142.1 ± 1.1 Torr). Each rat ran twice: in one bout the rat was allowed to reach itsspontaneous HR_max, which was 505 ± 7 and 501 ± 5 beats/min in hypoxic and normoxic exercise,respectively; in the other exercise bout,HR_max was increased by 20% to the preacclimatization value of 600 beats/min by atrial pacing. This resulted in an ~10% increase in_max, since theincrease in HR_max was offset by a10% decrease in stroke volume, probably due to shortening of diastolicfilling time. The increase in_max was accompanied by a proportionate increase in maximal rate of convective O₂ delivery(_max × arterial O₂ content), maximal workrate, and O_{2 max} inhypoxic and normoxic exercise. The data show that increasingHR_max topreacclimatization levels increasesO_{2 max}, supportingthe hypothesis that the lowHR_max tends to limitO_{2 max} after acclimatization to hypoxia.

     

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.

     

Quantitative analysis of transpleural flux in the isolated lung

Li, M. H., J. Hildebrandt, and M. P. Hlastala.Quantitative analysis of transpleural flux in the isolated lung.J. Appl. Physiol. 82(2): 545-551, 1997.In this study, the loss of inert gas through the pleura of anisolated ventilated and perfused rabbit lung was assessed theoreticallyand experimentally. A mathematical model was used to represent an idealhomogeneous lung placed within a box with gas flow(box) surrounding the lung. Thealveoli are assumed to be ventilated with room air(A) andperfused at constant flow () containinginert gases (x) with various perfusate-air partition coefficients(_p,x).The ratio of transpleural flux of gas(pl_x)to its total delivery to the lung via pulmonary artery( ),representing fractional losses across the pleura, can be shown todepend on four dimensionless ratios:1)_p,x,2) the ratio of alveolar ventilation to perfusion(A/), 3) the ratioof the pleural diffusing capacity(Dpl_x) to the conductance ofthe alveolar ventilation (Dpl_x /A_g,where _g is the capacitancecoefficient of gas), and 4) theratio of extrapleural (box) ventilation to alveolar ventilation(box/A).Experiments were performed in isolated perfused and ventilated rabbitlungs. The perfusate was a buffer solution containing six dissolvedinert gases covering the entire 10⁵-fold range of_p,x usedin the multiple inert gas elimination technique. Steady-state inert gasconcentrations were measured in the pulmonary arterial perfusate,pulmonary venous effluent, exhaled gas, and box effluent gas. Theexperimental data could be described satisfactorily by thesingle-compartment model. It is concluded that a simple theoreticalmodel is a useful tool for predicting transpleural flux from isolatedlung preparations, with known ventilation and perfusion, for inertgases within a wide range of .

     

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.

     

Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta -agonists

Carvalho, Paula, Shane R. Johnson, Nirmal B. Charan.Non-cAMP-mediated bronchial arterial vasodilation in response toinhaled -agonists. J. Appl.Physiol. 84(1): 215-221, 1998.We studied thedose-dependent effects of inhaled isoetharine HCl, a -adrenergicbronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow(br) in anesthetized sheep. Isoetharine resulted ina dose-dependent increase in br. With atotal dose of 17.5 mg, br increased from baselinevalues of 22 ± 3.4 (SE) to 60 ± 16 ml/min(P < 0.001), an effect independentof changes in cardiac output and systemic arterial pressure. To furtherstudy whether synthesis of endogenous nitric oxide (NO) affects-agonist-induced increases in br, weadministered isoetharine (20 mg) by inhalation before and after theNO-synthase inhibitorN-nitro-L-argininemethyl ester (L-NAME).Intravenous L-NAME (30 mg/kg) rapidly decreased br by ~80% of baseline,whereas L-NAME via inhalation(10 mg/kg) resulted in a delayed and smaller (~22%) decrease.Pretreatment with L-NAME viaboth routes of administration attenuated bronchial arterialvasodilation after subsequent challenge with isoetharine. We concludethat isoetharine via inhalation increases br in adose-dependent manner and that -agonist-induced relaxation ofvascular smooth muscle in the bronchial vasculature is partiallymediated via synthesis of NO.

     

Effect of prolonged, heavy exercise on pulmonary gas exchange in athletes

During maximalexercise, ventilation-perfusion inequality increases, especially inathletes. The mechanism remains speculative. Wehypothesized that, if interstitial pulmonary edema is involved, prolonged exercise would result in increasing ventilation-perfusion inequality over time by exposing the pulmonary vascular bed to highpressures for a long duration. The response to short-term exercise wasfirst characterized in six male athletes [maximal O₂ uptake(O_{2 max}) = 63 ml · kg¹ · min¹] by using 5 minof cycling exercise at 30, 65, and 90%O_{2 max}. Multiple inert-gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained. Resting log SD of the perfusion distribution (logSD) was normal [0.50 ± 0.03 (SE)] and increased with exercise (logSD = 0.65 ± 0.04, P < 0.005), alveolar-arterialO₂ difference increased (to 24 ± 3 Torr), and end-capillary pulmonary diffusion limitation occurred at 90%O_{2 max}. The subjectsrecovered for 30 min, then, after resting measurements were taken,exercised for 60 min at ~65%O_{2 max}.O₂ uptake, ventilation, cardiacoutput, and alveolar-arterial O₂difference were unchanged after the first 5 min of this test, but logSD increased from0.59 ± 0.03 at 5 min to 0.66 ± 0.05 at 60 min(P < 0.05), without pulmonary diffusion limitation. LogSD was negativelyrelated to total lung capacity normalized for body surface area(r = 0.97,P < 0.005 at 60 min). These data are compatible with interstitial edema as a mechanism and suggest that lungsize is an important determinant of the efficiency of gas exchangeduring exercise.

     

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.

     

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.

     

V/Q distribution and correlation to atelectasis in anesthetized paralyzed humans

Tokics, Leif, Göran Hedenstierna, Leif Svensson, BoBrismar, Torsten Cederlund, Hans Lundquist, and ÅkeStrandberg. / distributionand correlation to atelectasis in anesthetized paralyzed humans.J. Appl. Physiol. 81(4):1822-1833, 1996.Regional ventilation and perfusion were studiedin 10 anesthetized paralyzed supine patients by single-photon emissioncomputerized tomography. Atelectasis was estimated from twotransaxial computerized tomography scans. The ventilation-perfusion(/) distribution was alsoevaluated by multiple inert gas elimination. While the patients wereawake, inert gas / ratio wasnormal, and shunt did not exceed 1% in any patient. Computerizedtomography showed no atelectasis. During anesthesia, shunt ranged from0.4 to 12.2%. Nine patients displayed atelectasis (0.6-7.2% ofthe intrathoracic area), and shunt correlated with the atelectasis(r = 0.91, P < 0.001). Shunt was located independent lung regions corresponding to the atelectatic area. There wasconsiderable / mismatch, withventilation mainly of ventral lung regions and perfusion of dorsalregions. Little perfusion was seen in the most ventral parts (zone 1)of caudal (diaphragmatic) lung regions. In summary, shunt during anesthesia is due to atelectasis in dependent lung regions. The / distributions differ fromthose shown earlier in awake subjects.

     

Gas exchange and cardiovascular kinetics with different exercise protocols in heart transplant recipients

Grassi, Bruno, Claudio Marconi, Michael Meyer, Michel Rieu,and Paolo Cerretelli. Gas exchange and cardiovascular kinetics with different exercise protocols in heart transplant recipients. J. Appl. Physiol. 82(6): 1952-1962, 1997.Metabolicand cardiovascular adjustments to various submaximal exercises wereevaluated in 82 heart transplant recipients (HTR) and in 35 controlsubjects (C). HTR were tested 21.5 ± 25.3 (SD) mo (range1.0-137.1 mo) posttransplantation. Three protocols were used:protocol A consisted of 5 min of rectangular 50-W load repeatedtwice, 5 min apart [5 min rest, 5 min 50 W (Ex 1), 5 minrecovery, 5 min 50 W (Ex 2)]; protocol B consistedof 5 min of rectangular load at 25, 50, or 75 W; protocol Cconsisted of 15 min of rectangular load at 25 W. Breath-by-breathpulmonary ventilation (E),O₂ uptake (O₂),and CO₂ output(CO₂) were determined.During protocol A, beat-by-beat cardiacoutput () was estimated by impedance cardiography. The half times (t_1/2) of the on- andoff-kinetics of the variables were calculated. In all protocols,t_1/2 values forO₂ on-,E on-, andCO₂ on-kinetics were higher(i.e., the kinetics were slower) in HTR than in C, independently ofworkload and of the time posttransplantation. Also,t_1/2 on- was higher in HTRthan in C. In protocol A, no significant difference of t_1/2 O₂on- was observed in HTR between Ex 1 (48 ± 9 s) and Ex2 (46 ± 8 s), whereas t_1/2 on- was higher during Ex 1 (55 ± 24 s)than during Ex 2 (47 ± 15 s). In all protocols and for all variables, the t_1/2 off-values were higher in HTRthan in C. In protocol C, no differences of steady-stateE,O₂, andCO₂ were observed in bothgroups between 5, 10, and 15 min of exercise. We conclude that1) in HTR, a "priming" exercise, while effective inspeeding up the adjustment of convective O₂ flow to muscle fibers during a second on-transition, did not affect theO₂ on-kinetics, suggestingthat the slower O₂ on- inHTR was attributable to peripheral (muscular) factors; 2) thedissociation between on- andO₂ on-kinetics in HTRindicates that an inertia of muscle metabolic machinery is the mainfactor dictating theO₂ on-kinetics; and 3) theO₂ off-kinetics was slowerin HTR than in C, indicating a greater alactic O₂ deficitin HTR and, therefore, a sluggish muscleO₂ adjustment.

     

Age, fitness, and regional blood flow during exercise in the heat

Ho, C. W., J. L. Beard, P. A. Farrell, C. T. Minson, and W. L. Kenney. Age, fitness, and regional blood flow during exercisein the heat. J. Appl. Physiol. 82(4):1126-1135, 1997.During dynamic exercise in warm environments,the requisite increase in skin blood flow (SkBF) is supported by anincrease in cardiac output (c) and decreases insplanchnic (SBF) and renal blood flows (RBF). To examine interactionsbetween age and fitness in determining this integrated response, 24 men, i.e., 6 younger fit (YF), 6 younger sedentary (YS), 6 older fit (OF), and 6 older sedentary (OS) rested for 50 min, thenexercised at 35 and 60% maximalO₂ consumption(O_{2 max}) at36°C ambient temperature. YF had a significantly higherc and SkBF than any other group during exercise,but fitness level had no significant effect on any measured variable inthe older men. At 60%O_{2 max}, younger subjects had significantly greater decreases in SBF and RBF than theolder men, regardless of fitness level. Total flow redirected fromthese two vascular beds (SBF + RBF) followed YF >> YS > OF > OS. A rigorous 4-wk endurance training programincreased exercise SkBF in OS, but SBF and RBF were unchanged.Under these conditions, older men distribute cdifferently to regional circulations, i.e., smaller increases in SkBFand smaller decreases in SBF and RBF. In younger subjects, the higherSkBF associated with a higher fitness level is a function of both ahigher c and a greater redistribution of flow fromsplanchnic and renal circulations, but the attenuated splanchnic andrenal vasoconstriction in older men does not appear to change withenhanced aerobic fitness.

     

Pulmonary gas exchange during exercise in pigs

Increased ventilation-perfusion(A/)inequality is observed in ~50% of humans during heavy exercise andcontributes to the widening of the alveolar-arterialO₂ difference(A-aD_O2). Despite extensive investigation, the cause remains unknown. As a firststep to more direct examination of this problem, we developed an animalmodel. Eight Yucatan miniswine were studied at rest and duringtreadmill exercise at ~30, 50, and 85% of maximalO₂ consumption (O_{2 max}). Multipleinert-gas, blood-gas, and metabolic data were obtained. TheA-aD_O2increased from 0 ± 3 (SE) Torr at rest to 14 ± 2 Torr duringthe heaviest exercise level, but arterialPO₂(Pa_O2) remained at resting levels during exercise. There was normalA/inequality [log SD of the perfusion distribution(log) = 0.42 ± 0.04] at rest, and moderate increases(log = 0.68 ± 0.04, P < 0.0001) wereobserved with exercise. This result was reproducible on a separate day.TheA/inequality changes are similar to those reported in highly trainedhumans. However, in swine, unlike in humans, there was no inert gasevidence for pulmonary end-capillary diffusion limitation during heavyexercise; there was no systematic difference in the measuredPa_O2 and the Pa_O2 as predicted from the inertgases. These data suggest that the pig animal model iswell suited for studying the mechanism of exercise-inducedA/ inequality.

     

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.