Cervical magnetic stimulation as a method to discriminate between diaphragm and rib cage muscle fatigue

Inspiratory muscle fatigue can probablydetermine hypercapnic respiratory failure. Diaphragm fatigue isdetected by electrical phrenic stimulation (ELS), but there is nosimple tool to assess rib cage muscle (RCM) fatigue. Cervical magneticstimulation (CMS) costimulates the phrenic nerves and RCM. We reasonedthat changes in transdiaphragmatic pressure twitch (Pdi,tw) with CMSand ELS should be different after selective diaphragm vs. RCM fatigue. Five volunteers performed inspiratory resistive tasks while voluntarily uncoupling diaphragm and RCM. BaselinePdi,tw_ELS andPdi,tw_CMS were 28.57 ± 1.68 and 32.83 ± 2.92 cmH₂O. Afterselective diaphragm loading,Pdi,tw_ELS andPdi,tw_CMS were reduced by 39 and26%, with comparable decreases in gastric pressure twitch (Pga,tw).Esophageal pressure twitch (Pes,tw) was better preserved with CMS.Therefore Pes,tw/Pga,tw was lower with ELS than CMS (1.24 ± 0.16 vs. 1.73 ± 0.11, P = 0.05). After selectiveRCM loading, there was no diaphragm fatigue, butPes,tw_CMS was significantlyreduced (30%). These findings support the role of rib cagestiffening by CMS-related RCM contraction in the ELS-CMSdifferences and suggest that CMS can be used to assess RCM fatigue.

     

Effects of lung volume on diaphragm EMG signal strength during voluntary contractions

The use ofesophageal recordings of the diaphragm electromyogram (EMG) signalstrength to evaluate diaphragm activation during voluntary contractionsin humans has recently been criticized because of a possible artifactcreated by changes in lung volume. Therefore, the first aim of thisstudy was to evaluate whether there is an artifactual influence of lungvolume on the strength of the diaphragm EMG during voluntarycontractions. The second aim was to measure the required changes inactivation for changes in lung volume at a given tension, i.e., thevolume-activation relationship of the diaphragm. Healthy subjects(n = 6) performed contractions of thediaphragm at different transdiaphragmatic pressure (Pdi) targets (range20-160 cmH₂O) whilemaintaining chest wall configuration constant at different lungvolumes. The diaphragm EMG was recorded with a multiple-arrayesophageal electrode, with control of signal contamination andelectrode positioning. The effects of lung volume on the EMG werestudied by comparing the crural diaphragm EMG root mean square (RMS),an index of crural diaphragm activation, with an index of globaldiaphragm activation obtained by normalizing Pdi to the maximum Pdi atthe given muscle length(Pdi/Pdi_max@L) at thedifferent lung volumes. We observed a direct relationship between RMSand Pdi/Pdi_max@L independent of diaphragm length. The volume-activation relationship ofthe diaphragm was equally affected by changes in lung volume as thevolume-Pdi relationship (60% change from functional residual capacityto total lung capacity). We conclude that the RMS of the diaphragm EMGis not artifactually influenced by lung volume and can be used as areliable index of diaphragm activation. The volume-activationrelationship can be used to infer changes in the length-tensionrelationship of the diaphragm at submaximal activation/contractionlevels.

     

Aerobic fitness effects on exercise-induced low-frequency diaphragm fatigue

Babcock, Mark A., David F. Pegelow, Bruce D. Johnson, andJerome A. Dempsey. Aerobic fitness effects on exercise-induced low-frequency diaphragm fatigue. J. Appl.Physiol. 81(5): 2156-2164, 1996.We usedbilateral phrenic nerve stimulation (BPNS; at 1, 10, and 20 Hz atfunctional residual capacity) to compare the amount of exercise-induceddiaphragm fatigue between two groups of healthy subjects, a high-fitgroup [maximal O₂consumption (O_{2 max}) = 69.0 ± 1.8 ml ^· kg^{1 ·} min¹,n = 11] and a fit group(O_{2 max} = 50.4 ± 1.7 ml ^· kg^{1 ·} min¹,n = 13). Both groups exercised at88-92% O_{2 max}for about the same duration (15.2 ± 1.7 and 17.9 ± 2.6 min forhigh-fit and fit subjects, respectively,P > 0.05). The supramaximal BPNS test showed a significant reduction (P < 0.01) in the BPNS transdiaphragmatic pressure (Pdi) immediatelyafter exercise of 23.1 ± 3.1% for the high-fit group and23.1 ± 3.8% (P > 0.05)for the fit group. Recovery of the BPNS Pdi took 60 min in both groups.The high-fit group exercised at a higher absolute workload, whichresulted in a higher CO₂production (+26%), a greater ventilatory demand (+16%) throughout theexercise, and an increased diaphragm force output (+28%) over theinitial 60% of the exercise period. Thereafter, diaphragm force outputdeclined, despite a rising minute ventilation, and it was not differentbetween most of the high-fit and fit subjects. In summary, the high-fitsubjects showed diaphragm fatigue as a result of heavy enduranceexercise but were also partially protected from excessive fatigue,despite high ventilatory requirements, because their hyperventilatoryresponse to endurance exercise was reduced, their diaphragm wasutilized less in providing the total ventilatory response, and possiblytheir diaphragm aerobic capacity was greater.

     

Effect of chronically elevated CO2 on CA1 neuronal excitability

To study the effect of chronically elevated CO₂ on the excitability and function of neurons, we exposed mice to 7.5–8% CO₂ for 2 wk (starting at 2 days of age) and examined the properties of freshly dissociated hippocampal neurons. Neurons from control mice (CON) and from mice exposed to chronically elevated CO₂ had similar resting membrane potentials and input resistances. CO₂-exposed neurons, however, had a lower rheobase and a higher Na⁺ current density (580 ± 73 pA/pF; n = 27 neurons studied) than did CON neurons (280 ± 51 pA/pF, n = 34; P < 0.01). In addition, the conductance-voltage curve was shifted in a more negative direction in CO₂-exposed than in CON neurons (midpoint of the curve was –46 ± 3 mV for CO₂ exposed and –34 ± 3 mV for CON, P < 0.01), while the steady-state inactivation curve was shifted in a more positive direction in CO₂-exposed than in CON neurons (midpoint of the curve was –59 ± 2 mV for CO₂ exposed and –68 ± 3 mV for CON, P < 0.01). The time constant for deactivation at –100 mV was much smaller in CO₂-exposed than in CON neurons (0.8 ± 0.1 ms for CO₂ exposed and 1.9 ± 0.3 ms for CON, P < 0.01). Immunoblotting for Na⁺ channel proteins (subtypes I, II, and III) was performed on the hippocampus. Our data indicate that Na⁺ channel subtype I, rather than subtype II or III, was significantly increased (43%, n = 4; P < 0.05) in the hippocampi of CO₂-exposed mice. We conclude that in mice exposed to elevated CO₂, 1) increased neuronal excitability is due to alterations in Na⁺ current and Na⁺ channel characteristics, and 2) the upregulation of Na⁺ channel subtype I contributes, at least in part, to the increase in Na⁺ current density. sodium ion channels; oxygen deprivation     

Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo

Brown, Robert H., Wayne Mitzner, and Elizabeth M. Wagner.Interaction between airway edema and lung inflation onresponsiveness of individual airways in vivo. J. Appl.Physiol. 83(2): 366-370, 1997.Inflammatorychanges and airway wall thickening are suggested to cause increasedairway responsiveness in patients with asthma. In fivesheep, the dose-response relationships of individual airways weremeasured at different lung volumes to methacholine (MCh) before andafter wall thickening caused by the inflammatory mediator bradykininvia the bronchial artery. At 4 cmH₂O transpulmonary pressure(Ptp), 5 µg/ml MCh constricted the airways to a maximum of 18 ± 3%. At 30 cmH₂O Ptp, MCh resultedin less constriction (to 31 ± 5%). Bradykinin increased airwaywall area at 4 and 30 cmH₂O Ptp(159 ± 6 and 152 ± 4%, respectively;P < 0.0001). At 4 cmH₂O Ptp, bradykinin decreasedairway luminal area (13 ± 2%; P < 0.01), and the dose-response curve was significantly lower (P = 0.02). At 30 cmH₂O, postbradykinin, the maximalairway narrowing was not significantly different (26 ± 5%;P = 0.76). Bradykinin produced substantial airway wall thickening and slight potentiation ofthe MCh-induced airway constriction at low lung volume. At high lung volume, bradykinin increased wall thickness but had no effecton the MCh-induced airway constriction. We conclude that inflammatoryfluid leakage in the airways cannot be a primary cause of airwayhyperresponsiveness.

     

Crural diaphragm activation during dynamic contractions at various inspiratory flow rates

The purpose of this study was to evaluate the influence ofvelocity of shortening on the relationship between diaphragm activation and pressure generation in humans. This was achieved by relating theroot mean square (RMS) of the diaphragm electromyogram to thetransdiaphragmatic pressure (Pdi) generated during dynamic contractionsat different inspiratory flow rates. Five healthy subjects inspiredfrom functional residual capacity to total lung capacity at differentflow rates while reproducing identical Pdi and chest wall configurationprofiles. To change the inspiratory flow rate, subjects performed theinspirations while breathing across two different inspiratoryresistances (10 and 100 cmH₂O · l¹ · s),at mouth pressure targets of 10, 20, 40, and60 cmH₂O. The diaphragmelectromyogram was recorded and analyzed with control of signalcontamination and electrode positioning. RMS values obtained forinspirations with identical Pdi and chest wall configuration profileswere compared at the same percentage of inspiratory duration. Atinspiratory flows ranging between 0.1 and 1.4 l/s, there was nodifference in the RMS for the inspirations from functional residualcapacity to total lung capacity when Pdi and chest wall configurationprofiles were reproduced (n = 4). Athigher inspiratory flow rates, subjects were not able to reproducetheir chest wall displacements and adopted different recruitmentpatterns. In conclusion, there was no evidence for increased demand ofdiaphragm activation when healthy subjects breathe with similar chestwall configuration and Pdi profiles, at increasing flow rates up to 1.4 l/s.

     

Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs

To determine theinitial signaling event in the vascular permeability increase afterhigh airway pressure injury, we compared groups of lungs ventilated atdifferent peak inflation pressures (PIPs) with (gadolinium group) andwithout (control group) infusion of 20 µM gadolinium chloride, aninhibitor of endothelial stretch-activated cationchannels. Microvascular permeability was assessed by using the capillary filtration coefficient(K_fc), ameasure of capillary hydraulic conductivity.K_fc was measuredafter ventilation for 30-min periods with 7, 20, and 30 cmH₂O PIP with 3 cmH₂O positive end-expiratorypressure and with 35 cmH₂O PIPwith 8 cmH₂O positive end-expiratory pressure. In control lungs,K_fc increasedsignificantly to 1.8 and 3.7 times baseline after 30 and 35 cmH₂O PIP, respectively. In thegadolinium group,K_fc was unchangedfrom baseline (0.060 ± 0.010 ml · min¹ · cmH₂O¹ · 100 g¹) after any PIPventilation period. Pulmonary vascular resistance increasedsignificantly from baseline in both groups before the lastK_fc measurementbut was not different between groups. These results suggest thatmicrovascular permeability is actively modulated by a cellular responseto mechanical injury and that stretch-activated cation channels mayinitiate this response through increases in intracellular calciumconcentration.

     

Hypoxia, temperature, and pH/CO2 effects on respiratory discharge from a turtle brain stem preparation

Johnson, Stephen M., Rebecca A. Johnson, and Gordon S. Mitchell. Hypoxia, temperature, andpH/CO₂ effects on respiratory discharge from a turtle brain stem preparation. J. Appl. Physiol. 84(2): 649-660, 1998.An in vitrobrain stem preparation from adult turtles (Chrysemyspicta) was used to examine the effects of anoxia andincreased temperature and pH/CO₂on respiration-related motor output. At pH ~7.45, hypoglossal (XII)nerve roots produced patterns of rhythmic bursts (peaks) of discharge(0.74 ± 0.07 peaks/min, 10.0 ± 0.6 s duration) that werequantitatively similar to literature reports of respiratory activity inconscious, vagotomized turtles. Respiratory discharge was stable for 6 h at 22°C; at 32°C, peak amplitude and frequency progressivelyand reversibly decreased with time. Two hours of hypoxia had no effecton respiratory discharge. Acutely increasing bath temperature from 22 to 32°C decreased episode and peak duration and increased peakfrequency. Changes in pH/CO₂increased peak frequency from zero at pH 8.00-8.10 to maxima of0.81 ± 0.01 and 1.44 ± 0.02 peaks/min at 22°C (pH 7.32) and32°C (pH 7.46), respectively;pH/CO₂ sensitivity was similar atboth temperatures. We conclude that1) insensitivity to hypoxiaindicates that rhythmic discharge does not reflect gasping behavior,2) increased temperature altersrespiratory discharge, and 3)central pH/CO₂ sensitivity isunaffected by temperature in this preparation (i.e.,Q₁₀ ~1.0).

     

Effects of a synthetic lung surfactant on pharyngeal patency in awake human subjects

Van der Touw, T., A. B. H. Crawford, and J. R. Wheatley.Effects of a synthetic lung surfactant on pharyngeal patency inawake human subjects. J. Appl.Physiol. 82(1): 78-85, 1997.We examined theeffects of separate applications of saline and a synthetic lungsurfactant preparation (Surf; Exosurf Neonatal) into the supraglotticairway (SA) on the anteroposterior pharyngeal diameter(D_ap) and theairway pressures required to close (Pcl) and reopen (Pop) theSA in five awake normal supine subjects. D_ap, Pcl, and Popwere determined during lateral X-ray fluoroscopy and voluntary glotticclosure when pressure applied to the SA lumen was decreasedfrom 0 to 20 cmH₂O and thenincreased to +20 cmH₂O. After Surfapplication and relative to control,D_ap was largerfor most of the applied pressures, Pcl decreased (12.3 ± 1.9 to 18.7 ± 0.9 cmH₂O;P < 0.01), Pop decreased (13.4 ± 1.9 to 6.0 ± 3.4 cmH₂O;P < 0.01), and genioglossus electromyographic activity did not change (P > 0.05).Saline had no effect. These observations suggest that pharyngealintraluminal surface properties are important in maintaining pharyngealpatency. We propose that surfactants enhance pharyngeal patency byreducing surface tension and adhesive forces acting on intraluminal SAsurfaces.

     

LY-294002-inhibitable PI 3-kinase and regulation of baseline rates of Na(+) transport in A6 epithelia

Blocker-inducednoise analysis of epithelial Na⁺ channels (ENaCs) was usedto investigate how inhibition of an LY-294002-sensitive phosphatidylinositol 3-kinase (PI 3-kinase) alters Na⁺transport in unstimulated and aldosterone-prestimulated A6 epithelia. From baseline Na⁺ transport rates(I_Na) of 4.0 ± 0.1 (unstimulated) and9.1 ± 0.9 µA/cm² (aldosterone), 10 µM LY-294002caused, following a relatively small initial increase of transport, acompletely reversible inhibition of transport within 90 min to 33 ± 6% and 38 ± 2% of respective baseline values. Initialincreases of transport could be attributed to increases of channel openprobability (P_o) within 5 min to 143 ± 17% (unstimulated) and 142 ± 10% of control (aldosterone) frombaseline P_o averaging near 0.5. Inhibition oftransport was due to much slower decreases of functional channeldensities (N_T) to 28 ± 4% (unstimulated)and 35 ± 3% (aldosterone) of control at 90 min. LY-294002 (50 µM) caused larger but completely reversible increases ofP_o (215 ± 38% of control at 5 min) andmore rapid but only slightly larger decreases ofN_T. Basolateral exposure to LY-294002 induced nodetectable effect on transport, P_o or N_T. We conclude that an LY-294002-sensitive PI3-kinase plays an important role in regulation of transport bymodulating N_T and P_o ofENaCs, but only when presented to apical surfaces of the cells.

     

Alae nasi activation decreases nasal resistance during hyperoxic hypercapnia

It has beenproposed that decreases in nasal resistance (Rn) during hypercapnia areentirely due to vasoconstriction in the nasal cavity. We hypothesizedthat alae nasi (AN) muscle activity dilates the nasal vestibule andcontributes to the decrease in Rn during hypercapnia. Nine normalsubjects were studied during hyperoxic hypercapnia (HH). Rn andvestibular resistance (Rvest) for one nasal passage were measuredsimultaneously with the AN electromyogram before and after nasaldecongestion. HH decreased Rvest from 1.6 ± 0.6 to 0.8 ± 0.9 cmH₂O · l¹ · s(predecongestant) and from 1.3 ± 0.8 to 0.6 ± 0.7 cmH₂O · l¹ · s(postdecongestant; both P < 0.01).Nasal decongestant decreased Rn but not Rvest. Significant inverselinear relationships between Rvest and AN electromyogram weredemonstrated for all subjects. We conclude that in normal subjectsduring HH 1) decreases in Rvest arepredominantly due to increases in AN activity; and2) decreases in Rn are due to acombination of mucosal vasoconstriction and ANactivation.

     

Expiratory flow limitation and intrinsic positive end-expiratory pressure in obesity

Breathing at very low lung volumes might beaffected by decreased expiratory airflow and air trapping. Our purposewas to detect expiratory flow limitation (EFL) and, as a consequence, intrinsic positive end-expiratory pressure(PEEP_i) in grossly obesesubjects (OS). Eight OS with a mean body mass index (BMI) of 44 ± 5 kg/m² and six age-matchednormal-weight control subjects (CS) were studied in different bodypositions. Negative expiratory pressure (NEP) was used to determineEFL. In contrast to CS, EFL was found in two of eight OS in the uprightposition and in seven of eight OS in the supine position. DynamicPEEP_i and mean transdiaphragmatic pressure (mean Pdi) were measured in all six CS and in six of eight OS.In OS, PEEP_i increased from 0.14 ± 0.06 (SD) kPa in the upright position to 0.41 ± 0.11 kPa inthe supine position (P < 0.05) anddecreased to 0.20 ± 0.08 kPa in the right lateral position(P < 0.05, compared with supine),whereas, in CS, PEEP_i wassignificantly smaller (<0.05 kPa) in each position. In OS, mean Pdiin each position was significantly larger compared with CS. Mean Pdiincreased from 1.02 ± 0.32 kPa in the upright position to 1.26 ± 0.17 kPa in the supine position (not significant) and decreasedto 1.06 ± 0.26 kPa in the right lateral position(P < 0.05, compared with supine),whereas there were no significant changes in CS. We conclude that in OS1) tidal breathing can be affectedby EFL and PEEP_i;2) EFL andPEEP_i are promoted by the supineposture; and 3) the increaseddiaphragmatic load in the supine position is, in part, related toPEEP_i.

     

Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs

Parker, James C., and Claire L. Ivey.Isoproterenol attenuates high vascular pressure-inducedpermeability increases in isolated rat lungs. J. Appl.Physiol. 83(6): 1962-1967, 1997.To separate thecontributions of cellular and basement membrane components of thealveolar capillary barrier to the increased microvascular permeabilityinduced by high pulmonary venous pressures (Ppv), we subjected isolatedrat lungs to increases in Ppv, which increased capillary filtrationcoefficient(K_fc) withoutsignificant hemorrhage (31 cmH₂O)and with obvious extravasation of red blood cells (43 cmH₂O). Isoproterenol (20 µM)was infused in one group (Iso) to identify a reversible cellularcomponent of injury, and residual blood volumes were measured to assessextravasation of red blood cells through ruptured basement membranes.In untreated lungs (High Ppv group),K_fc increased 6.2 ± 1.3 and 38.3 ± 15.2 times baseline during the 31 and 43 cmH₂O Ppv states. In Iso lungs, K_fc was 36.2%(P < 0.05) and 64.3% of that in theHigh Ppv group at these Ppv states. Residual blood volumes calculatedfrom tissue hemoglobin contents were significantly increased by53-66% in the high Ppv groups, compared with low vascularpressure controls, but there was no significant difference between HighPpv and Iso groups. Thus isoproterenol significantly attenuatedvascular pressure-induced K_fc increases atmoderate Ppv, possibly because of an endothelial effect, but it did notaffect red cell extravasation at higher vascular pressures.

     

Effect of ingested sodium bicarbonate on muscle force, fatigue, and recovery

Verbitsky, O., J. Mizrahi, M. Levin, and E. Isakov.Effect of ingested sodium bicarbonate on muscle force, fatigue, and recovery. J. Appl. Physiol. 83(2):333-337, 1997.The influence of acute ingestion ofNaHCO₃ on fatigue and recovery ofthe quadriceps femoris muscle after exercise was studied in six healthymale subjects. A bicycle ergometer was used for exercising under three loading conditions: test A, loadcorresponding to maximal oxygen consumption; testB, load in test A + 17%; test C, load intest B but performed 1 h after acuteingestion of NaHCO₃.Functional electrical stimulation (FES) was applied to provokeisometric contraction of the quadriceps femoris. The resulting kneetorque was monitored during fatigue (2-min chronic FES) and recovery (10-s FES every 10 min, for 40 min). Quadriceps torques were higher inthe presence of NaHCO₃(P < 0.05): withNaHCO₃ the peak, residual, andrecovery (after 40 min) normalized torques were, respectively, 0.68 ± 0.05 (SD), 0.58 ± 0.05, and 0.73 ± 0.05; withoutNaHCO₃ the values were 0.45 ± 0.04, 0.30 ± 0.06, and 0.63 ± 0.06. The increasedtorques obtained after acute ingestion ofNaHCO₃ indicate the possibleexistence of improved nonoxidative glycolysis in isometric contraction,resulting in reduced fatigue and enhanced recovery.

     

Upper airway muscle activity and upper airway resistance in young adults during sleep

Henke, Kathe G. Upper airway muscle activity and upperairway resistance in young adults during sleep. J. Appl. Physiol. 84(2): 486-491, 1998.To determinethe relationship between upper airway muscle activity and upper airwayresistance in nonsnoring and snoring young adults, 17 subjects werestudied during sleep. Genioglossus and alae nasi electromyogramactivity were recorded. Inspiratory and expiratory supraglotticresistance (Rinsp and Rexp, respectively) were measured at peak flow,and the coefficients of resistance(K_insp andK_exp,respectively) were calculated. Data were recorded during control,with continuous positive airway pressure (CPAP), and on the breathimmediately after termination of CPAP. Rinsp during control averaged 7 ± 1 and 10 ± 2 cmH₂O · l¹ · sand K_inspaveraged 26 ± 5 and 80 ± 27 cmH₂O · l¹ · s²in the nonsnorers and snorers, respectively(P = not significant). Onthe breath immediately after CPAP,K_insp did notincrease over control in snorers (80 ± 27 for control vs. 46 ± 6 cmH₂O · l¹ · s²for the breath after CPAP) or nonsnorers (26 ± 5 vs. 29 ± 6 cmH₂O · l¹ · s²).These findings held true for Rinsp.K_exp did notincrease in either group on the breath immediately after termination ofCPAP. Therefore, 1) increases inupper airway resistance do not occur, despite reductions inelectromyogram activity in young snorers and nonsnorers, and2) increases in Rexp and expiratoryflow limitation are not observed in young snorers.

     

Age-related differences in Na+-dependent Ca2+ accumulation in rabbit hearts exposed to hypoxia and acidification

In this study, we test the hypothesisthat in newborn hearts (as in adults) hypoxia and acidificationstimulate increased Na⁺ uptake, in part via pH-regulatoryNa⁺/H⁺ exchange. Resulting increases inintracellular Na⁺ (Na_i) alter the force drivingthe Na⁺/Ca²⁺ exchanger and lead to increasedintracellular Ca²⁺. NMR spectroscopy measuredNa_i and cytosolic Ca²⁺ concentration([Ca²⁺]_i) and pH (pH_i) inisolated, Langendorff-perfused 4- to 7-day-old rabbit hearts. AfterNa⁺/K⁺ ATPase inhibition, hypoxic hearts gainedNa⁺, whereas normoxic controls did not [19 ± 3.4 to139 ± 14.6 vs. 22 ± 1.9 to 22 ± 2.5 (SE) meq/kg drywt, respectively]. In normoxic hearts acidified using theNH₄Cl prepulse, pH_i fell rapidly and recovered,whereas Na_i rose from 31 ± 18.2 to 117.7 ± 20.5 meq/kg dry wt. Both protocols caused increases in [Ca]_i;however, [Ca]_i increased less in newborn hearts than inadults (P < 0.05). Increases in Na_i and[Ca]_i were inhibited by theNa⁺/H⁺ exchange inhibitormethylisobutylamiloride (MIA, 40 µM; P < 0.05), aswell as by increasing perfusate osmolarity (+30 mosM) immediately before and during hypoxia (P < 0.05). The data supportthe hypothesis that in newborn hearts, like adults, increases inNa_i and [Ca]_i during hypoxia and afternormoxic acidification are in large part the result of increased uptakevia Na⁺/H⁺ and Na⁺/Ca²⁺exchange, respectively. However, for similar hypoxia and acidification protocols, this increase in [Ca]_i is less in newborn thanadult hearts.

     

Task failure with lack of diaphragm fatigue during inspiratory resistive loading in human subjects

McKenzie, D. K., G. M. Allen, J. E. Butler, and S. C. Gandevia. Task failure with lack of diaphragm fatigue during inspiratory resistive loading in human subjects. J. Appl. Physiol. 82(6): 2011-2019, 1997.Taskfailure during inspiratory resistive loading is thought to beaccompanied by substantial peripheral fatigue of the inspiratorymuscles. Six healthy subjects performed eight resistive breathingtrials with loads of 35, 50, 75 and 90% of maximal inspiratorypressure (MIP) with and without supplemental oxygen. MIP measuredbefore, after, and at every minute during the trial increased slightlyduring the trials, even when corrected for lung volume (e.g., for 24 trials breathing air, 12.5% increase, P < 0.05). In some trials, taskfailure occurred before 20 min (end point of trial), and in thesetrials there was an increase in end-tidalPCO₂(P < 0.01), despite the absence of peripheral muscle fatigue. In four subjects (6 trials with task failure), there was no decline in twitch amplitude with bilateral phrenic stimulation or in voluntary activation of the diaphragm, eventhough end-tidal PCO₂ rose by 1.6 ± 0.9%. These results suggest that hypoventilation,CO₂ retention, and ultimate taskfailure during resistive breathing are not simply dependent on impairedforce-generating capacity of the diaphragm or impaired voluntaryactivation of the diaphragm.

     

Regulation of the epithelial Na+ channel by intracellular Na+

The hypothesis that the intracellularNa⁺ concentration([Na⁺]_i)is a regulator of the epithelialNa⁺ channel (ENaC) was tested withthe Xenopus oocyte expression systemby utilizing a dual-electrode voltage clamp.[Na⁺]_iaveraged 48.1 ± 2.2 meq (n = 27)and was estimated from the amiloride-sensitive reversal potential.[Na⁺]_iwas increased by direct injection of 27.6 nl of 0.25 or 0.5 MNa₂SO₄.Within minutes of injection,[Na⁺]_istabilized and remained elevated at 97.8 ± 6.5 meq(n = 9) and 64.9 ± 4.4 (n = 5) meq 30 min after theinitial injection of 0.5 and 0.25 MNa₂SO₄,respectively. This increase of[Na⁺]_icaused a biphasic inhibition of ENaC currents. In oocytes injected with0.5 MNa₂SO₄(n = 9), a rapid decrease of inwardamiloride-sensitive slope conductance(g_Na) to 0.681 ± 0.030 of control within the first 3 min and a secondary, slowerdecrease to 0.304 ± 0.043 of control at 30 min were observed.Similar but smaller inhibitions were also observed with the injectionof 0.25 MNa₂SO₄.Injection of isotonicK₂SO₄(70 mM) or isotonicK₂SO₄made hypertonic with sucrose (70 mMK₂SO₄-1.2M sucrose) was without effect. Injection of a 0.5 M concentration ofeitherK₂SO₄,N-methyl-D-glucamine (NMDG) sulfate, or 0.75 M NMDG gluconate resulted in a much smaller initial inhibition (<14%) and little or no secondary decrease. Thusincreases of[Na⁺]_ihave multiple specific inhibitory effects on ENaC that can betemporally separated into a rapid phase that was complete within 2-3 min and a delayed slow phase that was observed between 5 and 30 min.

     

Recovery of diaphragmatic function in awake sheep after two approaches to thoracic surgery

Imanaka, Hideaki, William R. Kimball, John C. Wain, MasajiNishimura, Kenichi Okubo, Dean Hess, and Robert M. Kacmarek. Recovery of diaphragmatic function in awake sheep after two approaches to thoracic surgery. J. Appl.Physiol. 83(5): 1733-1740, 1997.Video-assistedthoracoscopic surgery (VATS) is replacing thoracotomy, but no study hasaddressed the extent or duration of VATS-induced diaphragmaticalteration. We hypothesized that VATS would impair diaphragmaticfunction less and return diaphragmatic function faster thanthoracotomy. In eight sheep, sonomicrometers were randomly implanted onthe right costal diaphragm via VATS or thoracotomy. Diaphragmaticresting length, shortening fraction, and respiratory function weremeasured weekly during quiet breathing (QB) andCO₂ rebreathing for 4 wk. ForVATS, shortening fraction was smallest onpostoperative days 1 (POD 1) (6.4 ± 3.4 and12.9 ± 8.7% during QB and 10%CO₂ rebreathing, respectively) and7 (6.3 ± 3.4 and 16.9 ± 4.0%during QB and 10% CO₂rebreathing, respectively) and recovered by 3 wk (13.2 ± 1.8 and28.9 ± 8.0% during QB and 10%CO₂ rebreathing, respectively).For thoracotomy, shortening fraction at 10%CO₂ rebreathing was smaller onPODs 1, 7, 14 (15.9 ± 7.1, 13.6 ± 5.4, and 19.0 ± 6.9%) than onPOD 28 (29.9 ± 8.2%), but notduring QB on POD 1 or7 (7.5 ± 3.8 and 3.4 ± 2.6%)compared with POD 28 (10.7 ± 8.7%). Shortening fraction did not differ between surgeries. There wasno group difference in minute ventilation, respiratory rate,transdiaphragmatic pressure, or esophageal and gastric pressures. Inconclusion, although shortening fraction recovered faster for VATS,this translated into insignificant functional differences.

     

Respiratory system mechanics in sedated, paralyzed, morbidly obese patients

Pelosi, P., M. Croci, I. Ravagnan, M. Cerisara, P. Vicardi,A. Lissoni, and L. Gattinoni. Respiratory system mechanics insedated, paralyzed, morbidly obese patients J. Appl.Physiol. 82(3): 811-818, 1997.The effects ofinspiratory flow and inflation volume on the mechanical properties ofthe respiratory system in eight sedated and paralyzed postoperativemorbidly obese patients (aged 37.6 ± 11.8 yr who had never smokedand had normal preoperative seated spirometry) were investigated byusing the technique of rapid airway occlusion during constant-flowinflation. With the patients in the supine position, we measured theinterrupter resistance (Rint,rs), which in humans probably reflectsairway resistance, the "additional" resistance (Rrs) due toviscoelastic pressure dissipation and time-constant inequalities, andstatic respiratory elastance (Est,rs). Intra-abdominalpressure (IAP) was measured by using a bladder catheter, and functionalresidual capacity was measured by the helium-dilution technique. Theresults were compared with a previous study on 16 normal anesthetizedparalyzed humans. Compared with normal persons, we found that in obesesubjects: 1) functional residualcapacity was markedly lower (0.645 ± 0.208 liter) and IAP washigher (24 ± 2.2 cmH₂O);2) alveolar-arterial oxygenationgradient was increased (178 ± 59 mmHg);3) the volume-pressure curve of therespiratory system was curvilinear with an "inflection" point;4) Est,rs, Rint,rs, and Rrs werehigher than normal (29.3 ± 5.04 cmH₂O/l, 5.9 ± 2.4 cmH₂O ^· l^{1 ·} s,and 6.4 ± 1.6 cmH₂O ^· l^{1 ·} s,respectively); 5) Rint,rs increasedwith increasing inspiratory flow, Est,rs did not change, and Rrsdecreased progressively; and 6) withincreasing inflation volume, Rint,rs and Est,rs decreased, whereasRrs rose progressively. Overall, our data suggest that obesesubjects during sedation and paralysis are characterized by hypoxemiaand marked alterations of the mechanical properties of the respiratorysystem, largely explained by a reduction in lung volume due to theexcessive unopposed IAP.