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 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.

     

Effects of CO2-HCO<SUP>&minus;</SUP><SUB>3</SUB> on catecholamine efflux from cat carotid body

Iturriaga, Rodrigo, and Julio Alcayaga. Effects ofCO₂-on catecholamine efflux from cat carotid body. J. Appl. Physiol. 84(1): 60-68, 1998.Using achronoamperometric technique with carbon-fiber microelectrodes andneural recordings, we simultaneously measured the effects of thefollowing procedures on catecholamine efflux (CA) andfrequency of chemosensory discharges (f_x) fromsuperfused cat carotid body: 1) theaddition ofCO₂- to Tyrode solution previously buffered withN-2-hydroxyethylpiperazine-N -2-ethanesulfonicacid, maintaining pH at 7.40; 2)hypercapnia (10% CO₂, pH 7.10);3) hypoxia(PO₂ h  40 Torr) with andwithoutCO₂-;and 4) the impact of several bolusesof dopamine (DA; 10-100 µg) on hypoxic and hypercapnic challenges. WithCO₂-,hypoxia increased f_x which preceded CAincreases, whereas hypercapnia raised f_x but didnot consistently increase CA. Repeated stimuli induced similarf_x increases, but attenuated CA. AfterDA, hypoxia produced larger CA, which preceded chemosensoryresponses. WithoutCO₂-, hypoxia produced a similar pattern of CA andf_x responses. Switching to Tyrode solution withCO₂-at pH 7.40 raised f_x but did not increase CA.WithCO₂- and after DA, hypoxic-induced CAs were larger than in its absence. Results suggest that DA release is not essential for chemosensory excitation.

     

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.

     

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 .

     

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.

     

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.

     

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.

     

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.

     

Absence of myofibrillar creatine kinase and diaphragm isometric function during repetitive activation

Creatine kinase(CK) provides ATP buffering in skeletal muscle and is expressed as1) cytosolic myofibrillar CK (M-CK)and 2) sarcomeric mitochondrial CK(ScCKmit) isoforms that differ in their subcellular localization. Wecompared the isometric contractile and fatigue properties of1) control CK-sufficient (Ctl),2) M-CK-deficient (M-CK[/]), and3) combined M-CK/ScCKmit-deficientnull mutant (CK[/]) diaphragm (Dia) todetermine the effect of the absence of M-CK activity on Dia performancein vitro. Baseline contractile properties were comparable across groupsexcept for specific force, which was ~16% lower inCK[/] Dia compared withM-CK[/] and Ctl Dia. During repetitiveactivation (40 Hz, duty cycle), force declined in all threegroups. This decline was significantly greater inCK[/] Dia compared with Ctl and M-CK[/] Dia. The pattern of forcedecline did not differ between M-CK[/] andCtl Dia. We conclude that Dia isometric muscle function is notabsolutely dependent on the presence of M-CK, whereas the completeabsence of CK acutely impairs isometric force generation duringrepetitive activation.

     

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.

     

Thermoregulatory responses to cold transients: effects of menstrual cycle in resting women

Effects of themenstrual cycle on heat loss and heat production(M) and core and skin temperatureresponses to cold were studied in six unacclimatized female nonsmokers(18-29 yr of age). Each woman, resting supine, was exposed to acold transient (ambient temperature = mean radiant temperature = 20 to5°C at 0.32°C/min, relative humidity = 50 ± 2%, wind speed = 1 m/s) in the follicular (F) phase(days 2-6) and midluteal (L)phase (days 19-23) of her menstrual cycle. Clothed in each of two ensembles with different thermal resistances, women performed multiple experiments in the F andL phases. Thermal resistance was 0.2 and 0.4 m² · K · W¹for ensembles A andB, respectively. Esophagealtemperature (T_es), mean weightedskin temperature(_sk),finger temperature (T_fing), andarea-weighted heat flux were recorded continuously. Rate of heat debt(S) and integrated mean bodytemperature(_b,i)were calculated by partitional calorimetry throughout the cold ramp. Extensive peripheral vasoconstriction in the F phase during early periods of the ramp elevated T_esabove thermoneutral levels. Shivering thermogenesis(M = M  M_basal,W /m²) was highly correlated withdeclines in_sk andT_fing(P <0.0001). There was a reducedslope in M as a function of_b,i inthe L phase with ensembles A(P < 0.02) andB (P < 0.01). Heat flux was higher andS was less in the L phases withensemble A(P < 0.05). An analytic modelrevealed that_sk andT_es contribute as additive inputsand T_fing has a multiplicativeeffect on the total control of Mduring cold transients(R² = 0.9).Endogenous hormonal levels at each menstrual cycle phase, coretemperature and_skinputs, vascular responses, and variations in body heat balance must beconsidered in quantifying thermoregulatory responses in women duringcold stress.

     

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.

     

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.

     

Fast and slow components of cerebral blood flow response to step decreases in end-tidal PCO2 in humans

This study examined the dynamics of the middlecerebral artery (MCA) blood flow response to hypocapnia in humans(n = 6) by using transcranial Dopplerultrasound. In a control protocol, end-tidalPCO₂(PET_CO2) was heldnear eucapnia (1.5 Torr above resting) for 40 min. In ahypocapnic protocol, PET_CO2was held near eucapnia for 10 min, then at 15 Torr below eucapnia for20 min, and then near eucapnia for 10 min. During both protocols,subjects hyperventilated throughout andPET_CO2 and end-tidalPO₂ were controlled by using thedynamic end-tidal forcing technique. Beat-by-beat values werecalculated for the intensity-weighted mean velocity (_IWM),signal power (), and theirinstantaneous product(_IWM).A simple model consisting of a delay, gain terms, time constants(_f,on, _f,off) and baseline levels offlow for the on- and off-transients, and a gain term(g_s) and time constant(_s) for a second slower component was fitted to the hypocapnic protocol. The cerebral bloodflow response to hypocapnia was characterized by a significant (P < 0.001) slowprogressive adaptation in_IWM, with g_s = 1.26 %/Torr and_s = 427 s, that persistedthroughout the hypocapnic period. Finally, the responses at the onsetand relief of hypocapnia were asymmetric(P < 0.001), with_f,on (6.8 s) faster than_f,off (14.3 s).

     

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.

     

Bronchial vasodilatory response to ionic and nonionic contrast media

Baile, Elisabeth M., Lu Wang, Lorraine Verburgt, and PeterD. Paré. Bronchial vasodilatory response to ionic andnonionic contrast media. J. Appl.Physiol. 82(3): 841-845, 1997.It has recentlybeen shown that bronchial arterial injection of conventional contrastmedium causes a significant increase in bronchial blood flow(br) and that this response is partially attenuatedafter infusion ofN-nitro-L-arginine(L-NNA). However, the precisemechanism for this increase in br is unknown. Inthis study we examined the effect of bronchial arterial injection ofconventional ionic as well as nonionic contrast media. We measuredbr in nine anesthetized, ventilated, open-chestsheep. br was recorded before (baseline) and at thepeak response to injection of 0.5 ml of either 0.9% saline (control;isosmolar with plasma), Omnipaque 300 (iohexol; nonionic), Conray 66 (sodium iothalamate; ionic), or 50% dextrose (viscouscontrol).

     

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.

     

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.

     

O2 uptake kinetics after acetazolamide administration during moderate- and heavy-intensity exercise

Inhibition of carbonic anhydrase (CA) isassociated with a lower plasma lactate concentration([La]_pl)during fatiguing exercise. We hypothesized that a lower[La]_plmay be associated with faster O₂uptake (O₂) kinetics during constant-load exercise. Seven men performed cycle ergometer exercise during control (Con) and acute CA inhibition with acetazolamide (Acz,10 mg/kg body wt iv). On 6 separate days, each subject performed 6-minstep transitions in work rate from 0 to 100 W (below ventilatory threshold,<ET)or to a O₂ corresponding to~50% of the difference between the work rate atET and peakO₂(>ET).Gas exchange was measured breath by breath. Trials were interpolated at1-s intervals and ensemble averaged to yield a single response. The mean response time (MRT, i.e., time to 63% of total exponential increase) for on- and off-transients was determined using a two- (<ET) or athree-component exponential model(>ET).Arterialized venous blood was sampled from a dorsal hand vein andanalyzed for[La]_pl.MRT was similar during Con (31.2 ± 2.6 and 32.7 ± 1.2 s for onand off, respectively) and Acz (30.9 ± 3.0 and 31.4 ± 1.5 s for on and off, respectively) for work rates<ET. Atwork rates >ET, MRTwas similar between Con (69.1 ± 6.1 and 50.4 ± 3.5 s for on andoff, respectively) and Acz (69.7 ± 5.9 and 53.8 ± 3.8 s for on and off, respectively). On- and off-MRTs were slower for>ET thanfor <ETexercise.[La]_plincreased above 0-W cycling values during<ET and>ET exercise but was lower at the end of the transition during Acz (1.4 ± 0.2 and 7.1 ± 0.5 mmol/l for<ET and>ET,respectively) than during Con (2.0 ± 0.2 and 9.8 ± 0.9 mmol/lfor <ETand >ET,respectively). CA inhibition does not affectO₂ utilization at the onset of<ET or>ETexercise, suggesting that the contribution of oxidative phosphorylationto the energy demand is not affected by acute CA inhibition with Acz.