Effects of N2O narcosis on breathing and effort sensations during exercise and inspiratory resistive loading

Fothergill, D. M., and N. A. Carlson. Effects ofN₂O narcosis on breathing andeffort sensations during exercise and inspiratory resistive loading.J. Appl. Physiol. 81(4):1562-1571, 1996.The influence of nitrous oxide(N₂O) narcosis on the responses toexercise and inspiratory resistive loading was studied in thirteen maleUS Navy divers. Each diver performed an incremental bicycle exercisetest at 1 ATA to volitional exhaustion while breathing a 23%N₂O gas mixture and a nonnarcoticgas of the same PO₂, density, andviscosity. The same gas mixtures were used during four subsequent30-min steady-state submaximal exercise trials in which the subjectsbreathed the mixtures both with and without an inspiratory resistance(5.5 vs. 1.1 cmH₂O ^· s ^· l¹at 1 l/s). Throughout each test, subjective ratings of respiratory effort (RE), leg exertion, and narcosis were obtained with acategory-ratio scale. The level of narcosis was rated between slightand moderate for the N₂O mixturebut showed great individual variation. Perceived leg exertion and thetime to exhaustion were not significantly different with the twobreathing mixtures. Heart rate was unaffected by the gas mixture andinspiratory resistance at rest and during steady-state exercise but wassignificantly lower with the N₂O mixture during incremental exercise (P < 0.05). Despite significant increases in inspiratory occlusionpressure (13%; P < 0.05),esophageal pressure (12%; P < 0.001), expired minute ventilation (4%;P < 0.01), and the work rate ofbreathing (15%; P < 0.001) when the subjects breathed the N₂O mixture,RE during both steady-state and incremental exercise was 25% lowerwith the narcotic gas than with the nonnarcotic mixture(P < 0.05). We conclude that the narcotic-mediated changes in ventilation, heart rate, and RE induced by23% N₂O are not of sufficientmagnitude to influence exercise tolerance at surface pressure.Furthermore, the load-compensating respiratory reflexes responsible formaintaining ventilation during resistive breathing are not depressed byN₂O narcosis.

     

Thermal and metabolic responses to cold-water immersion at knee, hip, and shoulder levels

Lee, Dae T., Michael M. Toner, William D. McArdle, IoannisS. Vrabas, and Kent B. Pandolf. Thermal and metabolic responses tocold-water immersion at knee, hip, and shoulder levels.J. Appl. Physiol. 82(5):1523-1530, 1997.To examine the effect of cold-water immersion atdifferent depths on thermal and metabolic responses, eight men (25 yrold, 16% body fat) attempted 12 tests: immersed to the knee (K), hip(H), and shoulder (Sh) in 15 and 25°C water during both rest (R) orleg cycling [35% peak oxygen uptake; (E)] for up to 135 min. At 15°C, rectal (T_re)and esophageal temperatures(T_es) between R and E were notdifferent in Sh and H groups (P > 0.05), whereas both in K group were higher during E than R(P < 0.05). At 25°C,T_re was higher(P < 0.05) during E than R at alldepths, whereas T_es during E washigher than during R in H and K groups.T_re remained at control levels inK-E at 15°C, K-E at 25°C, and in H-E groups at 25°C,whereas T_es remained unchanged inK-E at 15°C, in K-R at 15°C, and in all 25°C conditions (P > 0.05). During R and E, themagnitude of T_re change wasgreater (P < 0.05) than themagnitude of T_es change in Sh andH groups, whereas it was not different in the K group(P > 0.05). Total heat flow wasprogressive with water depth. During R at 15 and 25°C, heatproduction was not increased in K and H groups from control level(P > 0.05) but it did increase in Shgroup (P < 0.05). The increase inheat production during E compared with R was smaller(P < 0.05) in Sh (121 ± 7 W/m² at 15°C and 97 ± 6 W/m² at 25°C) than in H (156 ± 6 and 126 ± 5 W/m²,respectively) and K groups (155 ± 4 and 165 ± 6 W/m², respectively). These datasuggest that T_re andT_es respond differently duringpartial cold-water immersion. In addition, water levels above knee in15°C and above hip in 25°C cause depression of internal temperatures mainly due to insufficient heat production offsetting heatloss even during light exercise.

     

Exercise-associated hyponatremia in Alaskan sled dogs: urinary and hormonal responses

Hinchcliff, K. W., G. A. Reinhart, J. R. Burr, R. A. Swenson. Exercise-associated hyponatremia in Alaskansled dogs: urinary and hormonal responses. J. Appl.Physiol. 83(3): 824-829, 1997.Exercise-associated hyponatremia occurs in horses and humans, both species that sweat, and in sled dogs, which do not sweat. Toinvestigate the mechanism of exercise-associated hyponatremia in sleddogs, we measured water turnover, serum electrolyte concentrations andosmolality, plasma renal hormone concentrations, and urine compositionof 12 fit Alaskan sled dogs before, during, and after a 490-km sled dograce (Ex group). Water turnover and serum electrolyte concentrationswere measured in six similarly fit dogs that did not run (Sed group).Water turnover was significantly larger(P < 0.001) in Ex [190 ± 19 (SD)ml · kg¹ · day¹]than in Sed dogs (51 ± 13 ml · kg¹ · day¹).There were significant (P < 0.001)decreases in serum sodium concentration (from 148.6 ± 2.8 to 139.7 ± 1.9 mmol/l) and osmolality (from 306 ± 9 to 296 ± 5 mosmol/kgH₂O) of Ex, but not Sed,dogs during the race. Plasma concentrations of arginine vasopressin decreased, whereas aldosterone and plasma renin activity increased significantly (P < 0.01) during therace. Urine osmolality was unchanged, whereas urine sodium, potassium,and chloride concentrations decreased significantly(P < 0.05) and urine ureaconcentration increased (P = 0.06).These results demonstrate increased water turnover associated withhyponatremia and renal sodium conservation with maintained high urineosmolality in exercising Alaskan sled dogs.

     

Skeletal muscle chemoreflex and pHi in exercise ventilatory control

Oelberg, David A., Allison B. Evans, Mirko I. Hrovat, PaulP. Pappagianopoulos, Samuel Patz, and David M. Systrom. Skeletal muscle chemoreflex and pH_i inexercise ventilatory control. J. Appl.Physiol. 84(2): 676-682, 1998.To determinewhether skeletal muscle hydrogen ion mediates ventilatory drive inhumans during exercise, 12 healthy subjects performed three bouts ofisotonic submaximal quadriceps exercise on each of 2 days in a 1.5-Tmagnet for ³¹P-magnetic resonancespectroscopy(³¹P-MRS). Bilaterallower extremity positive pressure cuffs were inflated to 45 Torr duringexercise (BLPP_ex) or recovery(BLPP_rec) in a randomized orderto accentuate a muscle chemoreflex. Simultaneous measurements were madeof breath-by-breath expired gases and minute ventilation, arterializedvenous blood, and by ³¹P-MRS ofthe vastus medialis, acquired from the average of 12 radio-frequencypulses at a repetition time of 2.5 s. WithBLPP_ex, end-exercise minuteventilation was higher (53.3 ± 3.8 vs. 37.3 ± 2.2 l/min;P < 0.0001), arterializedPCO₂ lower (33 ± 1 vs. 36 ± 1 Torr; P = 0.0009), and quadricepsintracellular pH (pH_i) more acid (6.44 ± 0.07 vs. 6.62 ± 0.07; P = 0.004), compared withBLPP_rec. Bloodlactate was modestly increased withBLPP_ex but without a change inarterialized pH. For each subject, pH_i was linearly relatedto minute ventilation during exercise but not to arterialized pH. Thesedata suggest that skeletal muscle hydrogen ion contributes to theexercise ventilatory response.

     

Furosemide reduces accumulated oxygen deficit in horses during brief intense exertion

Hinchcliff, K. W., K. H. McKeever, W. W. Muir, and R. A. Sams. Furosemide reduces accumulated oxygen deficit inhorses during brief intense exertion. J. Appl.Physiol. 81(4): 1550-1554, 1996.We theorizedthat furosemide-induced weight reduction would reduce the contributionof anaerobic metabolism to energy expenditure of horses during intenseexertion. The effects of furosemide on accumulatedO₂ deficit and plasma lactateconcentration of horses during high-intensity exercise were examined ina three-way balance randomized crossover study. Nine horses completedeach of three trials: 1) a control(C) trial, 2) a furosemide-unloaded(FU) trial in which the horse received furosemide 4 h before running, and 3) a furosemide weight-loaded(FL) trial during which the horse received furosemide and carriedweight equal to the weight lost after furosemide administration. Horsesran for 2 min at ~120% maximalO₂ consumption. Furosemide (FU)increased O₂ consumption (ml ^· 2 min^{1 ·} kg¹)compared with C (268 ± 9 and 257 ± 9, P < 0.05), whereas FL was notdifferent from C (252 ± 8). AccumulatedO₂ deficit (ml O₂ equivalents/kg) wassignificantly (P < 0.05) lowerduring FU (81.2 ± 12.5), but not during FL (96.9 ± 12.4), thanduring C (91.4 ± 11.5). Rate of increase in blood lactateconcentration (mmol ^· 2 min^{1 ·} kg¹)after FU (0.058 ± 0.001), but not after FL (0.061 ± 0.001), was significantly (P < 0.05) lower than after C (0.061 ± 0.001). Furosemide decreased theaccumulated O₂ deficit and rate ofincrease in blood lactate concentration of horses during briefhigh-intensity exertion. The reduction in accumulatedO₂ deficit in FU-treated horseswas attributable to an increase in the mass-specific rate ofO₂ consumption during thehigh-intensity exercise test.

     

Conservation of bronchiolar wall area during constriction and dilation of human airways

Mitchell, R. W., E. Rühlmann, H. Magnussen, N. M. Muñoz, A. R. Leff, and K. F. Rabe. Conservation ofbronchiolar wall area during constriction and dilation of humanairways. J. Appl. Physiol. 82(3):954-958, 1997.We assessed the effect of smooth musclecontraction and relaxation on airway lumen subtended by the internalperimeter(A_i)and total cross-sectional area (A_o)of human bronchial explants in the absence of the potential lungtethering forces of alveolar tissue to test the hypothesis thatbronchoconstriction results in a comparable change ofA_i andA_o.Luminal area (i.e.,A_i) andA_owere measured by using computerized videomicrometry, and bronchial wallarea was calculated accordingly. Images on videotape were captured;areas were outlined, and data were expressed as internal pixel numberby using imaging software. Bronchial rings were dissected in 1.0- to1.5-mm sections from macroscopically unaffected areas of lungs frompatients undergoing resection for carcinoma, placed in microplate wellscontaining buffered saline, and allowed to equilibrate for 1 h.Baseline, A_o[5.21 ± 0.354 (SE)mm²], andA_i(0.604 ± 0.057 mm²) weremeasured before contraction of the airway smooth muscle (ASM) withcarbachol. MeanA_inarrowed by 0.257 ± 0.052 mm²in response to 10 µM carbachol (P = 0.001 vs. baseline). Similarly, A_onarrowed by 0.272 ± 0.110 mm²in response to carbachol (P = 0.038 vs. baseline; P = 0.849 vs. change inA_i).Similar parallel changes in cross-sectional area forA_iandA_owere observed for relaxation of ASM from inherent tone of otherbronchial rings in response to 10 µM isoproterenol. We demonstrate aunique characteristic of human ASM; i.e., both luminal and totalcross-sectional area of human airways change similarly on contractionand relaxation in vitro, resulting in a conservation of bronchiolarwall area with bronchoconstriction and dilation.

     

A model for phosphocreatine resynthesis

Nevill, Alan M., David A. Jones, David McIntyre, Gregory C. Bogdanis, and Mary E. Nevill. A model forphosphocreatine resynthesis. J. Appl.Physiol. 82(1): 329-335, 1997.A model for phosphocreatine (PCr) resynthesis is proposed based on a simple electric circuit, where the PCr store in muscle is likened to thestored charge on the capacitor. The solution to the second-order differential equation that describes the potential around the circuitsuggests the model for PCr resynthesis is given byPCr(t) = R  [d₁ ^· exp(k₁ ^· t) ± d₂ ^· exp(k₂ ^· t)],where R is PCr concentration at rest,d₁,d₂, k₁, andk₂ are constants, andt is time. By using nonlinear leastsquares regression, this double-exponential model was shown to fit thePCr recovery data taken from two studies involving maximal exerciseaccurately. In study 1, when themuscle was electrically stimulated while occluded, PCr concentrations rose during the recovery phase to a level above that observed at rest.In study 2, after intensive dynamicexercise, PCr recovered monotonically to resting concentrations. Thesecond exponential term in the double-exponential model was found tomake a significant additional contribution to the quality of fit inboth study 1 (P < 0.05) andstudy 2 (P < 0.01).

     

Effects of training duration on substrate turnover and oxidation during exercise

Phillips, S. M., H. J. Green, M. A. Tarnopolsky, G. J. F. Heigenhauser, R. E. Hill, and S. M. Grant. Effects of training duration on substrate turnover and oxidation during exercise. J. Appl. Physiol. 81(5):2182-2191, 1996.Adaptations in fat and carbohydrate metabolismafter a prolonged endurance training program were examined using stableisotope tracers of glucose([6,6-²H₂]glucose),glycerol([²H₅]glycerol),and palmitate([²H₂]palmitate).Active, but untrained, males exercised on a cycle for 2 h/day[60% pretraining peak O₂consumption (O_{2 peak}) = 44.3 ± 2.4 ml ^· kg^{1 ·} min¹]for a total of 31 days. Three cycle tests (90 min at 60% pretraining O_{2 peak}) wereadministered before training (PRE) and after 5 (5D) and 31 (31D) daysof training. Exercise increased the rate of glucose production(R_a) and utilization(R_d) as well as the rate oflipolysis (glycerol R_a) and freefatty acid turnover (FFA R_a/R_d).At 5D, training induced a 10% (P < 0.05) increase in total fat oxidation because of an increase inintramuscular triglyceride oxidation (+63%,P < 0.05) and a decreased glycogenoxidation (16%, P < 0.05).At 31D, total fat oxidation during exercise increased a further 58%(P < 0.01). The pattern of fatutilization during exercise at 31D showed a reduced reliance on plasmaFFA oxidation (FFA R_d) and agreater dependence on oxidation of intramuscular triglyceride, whichincreased more than twofold (P < 0.001). In addition, glucose R_aand R_d were reduced at all timepoints during exercise at 31D compared with PRE and 5D. We concludethat long-term training induces a progressive increase in fatutilization mediated by a greater oxidation of fats from intramuscularsources and a reduction in glucose oxidation. Initial changes arepresent as early as 5D and occur before increases in muscle maximalmitochondrial enzyme activity [S. M. Phillips, H. J. Green, M. A. Tarnopolsky, G. J. F. Heigenhauser, and S. M. Grant.Am. J. Physiol. 270 (Endocrinol. Metab. 33):E265-E272, 1996].

     

Hypoxia- and normoxia-induced reversibility of autonomic control in Andean guinea pig heart

León-Velarde, Fabiola, Jean-Paul Richalet, Juan-CarlosChavez, Rachid Kacimi, Maria Rivera-Chira, José-Antonio Palacios, and Daniel Clark. Hypoxia- and normoxia-induced reversibility ofautonomic control in Andean guinea pig heart. J. Appl.Physiol. 81(5): 2229-2234, 1996.We hereindescribe the regulation of cardiac receptors in a typical high-altitudenative animal. Heart rate response to isoproterenol(HR_Iso)(beats ^· min^{1 ·} mgIso ^· kg¹)and atropine, the density of -adrenergic(_AR) and muscarinic (M₂) receptors, and theventricular content of norepinephrine (NE) and dopamine (DA) werestudied in guinea pigs (Caviaporcellus). Animals native to Lima, Peru (150 m) werestudied at sea level (SL) and after 5 wk at 4,300-m altitude (SL-HA).Animals native to Rancas [Pasco, Peru (4,300 m)] werestudied at high altitude (HA) and after 5 wk at SL (HA-SL). HA animalshad a lower HR_Iso, maximum numberof _AR binding sites(B_max),_AR dissociation constant (K_d), NE, andDA (P < 0.05) and a higherM₂B_max(P < 0.001) when compared with theSL group. HA-SL showed an increase of theHR_Iso, _ARK_d, and NE(P < 0.05) and a decrease of theM₂B_max andK_d (P < 0.0001) when compared with theHA group. The present study demonstrates the differential regulationand reversibility of the autonomic control in the guinea pig heart.

     

Secretory modulation of basolateral membrane inwardly rectified K(+) channel in guinea pig distal colonic crypts

Cell-attached recordings revealedK⁺ channel activity in basolateral membranes ofguinea pig distal colonic crypts. Inwardly rectified currents wereapparent with a pipette solution containing 140 mM K⁺.Single-channel conductance () was 9 pS at the resting membrane potential. Another inward rectifier with  of 19 pS was observed occasionally. At a holding potential of 80 mV,  was 21 and 41 pS,respectively. Identity as K⁺ channels was confirmed afterpatch excision by changing the bath ion composition. From reversalpotentials, relative permeability of Na⁺ overK⁺ (P_Na/P_K)was 0.02 ± 0.02, withP_Rb/P_K = 1.1 andP_Cl/P_K < 0.03. Spontaneous open probability (P_o) of the 9-pSinward rectifier (^gpK_ir) was voltageindependent in cell-attached patches. Both a low(P_o = 0.09 ± 0.01) and a moderate(P_o = 0.41 ± 0.01) activity mode wereobserved. Excision moved ^gpK_ir to the mediumactivity mode; P_o of^gpK_ir was independent of bath Ca²⁺activity and bath acidification. Addition of Cl andK⁺ secretagogues altered P_o of^gpK_ir. Forskolin or carbachol (10 µM)activated the small-conductance ^gpK_ir inquiescent patches and increased P_o inlow-activity patches. K⁺ secretagogues, either epinephrine(5 µM) or prostaglandin E₂ (100 nM), decreasedP_o of ^gpK_ir in activepatches. This ^gpK_ir may be involved inelectrogenic secretion of Cl and K⁺ acrossthe colonic epithelium, which requires a large basolateral membraneK⁺ conductance during maximal Cl secretionand, presumably, a lower K⁺ conductance during primaryelectrogenic K⁺ secretion.

     

Respiratory tissue properties derived from flow transfer function in healthy humans

Tomalak, W., R. Peslin, and C. Duvivier. Respiratorytissue properties derived from flow transfer function in healthy humans. J. Appl. Physiol. 82(4):1098-1106, 1997.Assuming homogeneity of alveolar pressure, therelationship between airway flow and flow at the chest during forcedoscillation at the airway opening [flow transfer function(FTF)] is related to lung and chest wall tissue impedance (Zti):FTF = 1 + Zti/Zg, where Zg is alveolar gas impedance, which isinversely proportional to thoracic gas volume. By using a flow-typebody plethysmograph to obtain flow rate at body surface, FTF has beenmeasured at oscillation frequencies (f_os) of 10, 20, 30 and 40 Hz in eight healthy subjects during both quiet and deepbreathing. The data were corrected for the flow shunted through upperairway walls and analyzed in terms of tissue resistance (Rti) andeffective elastance (Eti,eff) by using plethysmographically measuredthoracic gas volume values. In most subjects, Rti was seen to decreasewith increasingf_os and Eti,effto vary curvilinearly withf_os²,which is suggestive of mechanical inhomogeneity. Rti presented a weakvolume dependence during breathing, variable in sign according tof_os and amongsubjects. In contrast, Eti,eff usually exhibited a U-shaped patternwith a minimum located a little above or below functional residualcapacity and a steep increase with decreasing or increasing volume(30-80 hPa/l²) on eitherside. These variations are in excess of those expected from the sigmoidshape of the static pressure-volume curve and may reflect the effect ofrespiratory muscle activity. We conclude that FTF measurement is aninteresting tool to study Rti and Eti,eff and that these parametershave probably different physiological determinants.

     

Diaphragm thickening during inspiration

Cohn, David, Joshua O. Benditt, Scott Eveloff, and F. DennisMcCool. Diaphragm thickening during inspiration.J. Appl. Physiol. 83(1): 291-296, 1997.Ultrasound has been used to measure diaphragm thickness(T_di) in thearea where the diaphragm abuts the rib cage (zone of apposition).However, the degree of diaphragm thickening during inspiration reportedas obtained by one-dimensional M-mode ultrasound was greater than thatpredicted by using other radiographic techniques. Becausetwo-dimensional (2-D) ultrasound provides greater anatomic definitionof the diaphragm and neighboring structures, we used this technique toreevaluate the relationship between lung volume andT_di. We firstestablished the accuracy and reproducibility of 2-D ultrasound bymeasuring T_diwith a 7.5-MHz transducer in 26 cadavers. We found thatT_di measured byultrasound correlated significantly with that measured by ruler (R² = 0.89), withthe slope of this relationship approximating a line of identity(y = 0.89x + 0.04 mm). The relationship between lung volume andT_di was thenstudied in nine subjects by obtaining diaphragm images at the fivetarget lung volumes [25% increments from residual volume (RV) tototal lung capacity (TLC)]. Plots ofT_di vs. lungvolume demonstrated that the diaphragm thickened as lung volumeincreased, with a more rapid rate of thickening at the higher lungvolumes[T_di = 1.74 vital capacity (VC)² + 0.26 VC + 2.7 mm] (R² = 0.99; P < 0.001) where lung volumeis expressed as a fraction of VC. The mean increase inT_di between RVand TLC for the group was 54% (range 42-78%). We conclude that2-D ultrasound can accurately measureT_di and that theaverage thickening of the diaphragm when a subject is inhaling from RVto TLC using this technique is in the range of what would be predictedfrom a 35% shortening of the diaphragm.

     

Esophageal PCO2 as a monitor of perfusion failure during hemorrhagic shock

Sato, Yoji, Max Harry Weil, Wanchun Tang, Shijie Sun,Jianlin Xie, Joe Bisera, and Hidehiro Hosaka. EsophagealPCO₂ as a monitor of perfusionfailure during hemorrhagic shock. J. Appl.Physiol. 82(2): 558-562, 1997.Measurement ofgastric wall PCO₂(Pg_CO2) bytonometric method has emerged as an attractive option for estimatingvisceral perfusion during circulatory shock. However, gastric acidsecretion obfuscates the tonometric measurement. We, therefore,investigated the option of measuringPCO₂ in the esophagus to minimizethese restraints. Hemorrhagic shock was induced in five Sprague-Dawleyrats, and five rats served as sham controls.Pg_CO2 wasmeasured with an ion-sensitive field effect transistor that wassurgically implanted into the gastric wall. Esophageal luminalPCO₂(Pe_CO2) wasmeasured by a second ion-sensitive field effect transistor sensor.During hemorrhagic shock, mean aortic pressure declined from 150 to 50 mmHg. Gastric blood flow decreased from 58 to 12 ml ^· min^{1 ·} 100 g¹ (21% of preshock) andesophageal blood flow from 44 to 7 ml ^· min^{1 ·} 100 g¹ (16% of preshock).Pg_CO2simultaneously increased from 47 to 116 Torr andPe_CO2 from 47 to 127 Torr. The increases inPg_CO2 werehighly correlated with increases inPe_CO2(r = 0.90). Esophageal tonometry may,therefore, serve as a practical alternative to gastric tonometry.

     

Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ETB receptors

Dupuis, Jocelyn, Carl A. Goresky, and Alain Fournier.Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ET_B receptors.J. Appl. Physiol. 81(4):1510-1515, 1996.The pulmonary circulation plays an importantrole in the removal of circulating endothelin-1 (ET-1). Plasma ET-1levels are increased in pulmonary hypertensive states of variousetiologies (e.g., idiopathic, heart failure, and congenital anomalies)in proportion to the severity of pulmonary hypertension. It is possible that reduced pulmonary clearance of this peptide contributes to thehyperendothelinemia of those pathologies. TheET_A andET_B receptors are abundant in lungtissues: on the vascular endothelium, theET_B receptor is predominant andmay contribute to ET-1 extraction through receptor-mediatedendocytosis. We designed experiments to determine and quantify theimportance of the ET_A andET_B receptors in the pulmonaryextraction of circulating ET-1 in anesthetized dogs. The single-passcumulative tracer ET-1 extraction by the lung was measured with theindicator-dilution technique before and 5 min after intrapulmonaryinjection of the specific ET_Aantagonist BQ-123 (n = 5, 120-960nmol) and the specific ET_Bantagonist BQ-788 (n = 6, 1,000 nmol).The inhibitors had no significant effect on pulmonary and systemichemodynamics. Mean cumulative pulmonary ET-1 extraction was notmodified by BQ-123 [control (C): 36 ± 4%, antagonist (A): 34 ± 6%] but was completely abolished by BQ-788 (C: 34 ± 6%, A: 0 ± 2%, P < 0.001). Thepulmonary rate constant (K) for ET-1removal was also unaffected by BQ-123 (C: 0.050 ± 0.0085 s¹, A: 0.047 ± 0.012 s¹) but significantlydecreased and became close to zero after BQ-788 (C: 0.058 ± 0.014 s¹, A: 0.009 ± 0.007 s¹,P < 0.001). We conclude that theET_B receptor is completely andexclusively responsible for pulmonary ET-1 removal in vivo. Futurestudies are needed to show whether desensitization or downregulation ofthe ET_B receptor may contribute tothe increase in circulating ET-1 levels in conditions associated withpulmonary hypertension. This novel pulmonary endothelial cell functionmay play a protective role by modulating circulating ET-1 levels in thesystemic circulation.

     

Pliometric contraction-induced injury of mouse skeletal muscle: effect of initial length

Hunter, Kam D., and John A. Faulkner. Pliometriccontraction-induced injury of mouse skeletal muscle: effect of initial length. J. Appl. Physiol. 82(1):278-283, 1997.For single pliometric (lengthening) contractionsinitiated from optimal fiber length (L_f), the mostimportant factor determining the subsequent force deficit is the workinput during the stretch. We tested the hypothesis that regardless ofthe initial length, the force deficit is primarily a function of thework input. Extensor digitorum longus muscles of mice were maximallyactivated in situ and lengthened at 2 L_f /s from oneof three initial fiber lengths (90, 100, or 120% of L_f) to one ofthree final fiber lengths (150, 160, or 170% of L_f). Maximalisometric force production was assessed before and after the pliometriccontraction. No single mechanical factor, including thework input(r² = 0.34), was sufficient to explain the differences in force deficits observed among groups. Therefore, the force deficit appears to arisefrom a complex interaction of mechanicalevents. With the data grouped by initial fiber length,the correlation between the average work and the average force deficitwas high(r² = 0.97-0.99). Consequently, differences in force deficits among groups were best explained on the basis of the initial fiber length andthe work input during the stretch.

     

Effects of the ovarian cycle on sympathetic neural outflow during static exercise

We comparedreflex responses to static handgrip at 30% maximal voluntarycontraction (MVC) in 10 women (mean age 24.1 ± 1.7 yr) during twophases of their ovarian cycle: the menstrual phase (days 1-4) and the follicularphase (days10-12). Changes in muscle sympathetic nerve activity (MSNA; microneurography) in response tostatic exercise were greater during the menstrual compared withfollicular phase (phase effect P = 0.01). Levels of estrogen were less during the menstrual phase(75 ± 5.5 vs. 116 ± 9.6 pg/ml, days 1-4 vs.days 10-12;P = 0.002). Generated tension did not explain differences in MSNA responses (MVC: 29.3 ± 1.3 vs. 28.2 ± 1.5 kg, days 1-4 vs.days 10-12;P = 0.13). In a group of experiments with the use of ³¹P-NMRspectroscopy, no phase effect was observed forH⁺ andH₂PO₄ concentrations(n = 5). During an ischemicrhythmic handgrip paradigm (20% MVC), a phase effect was notobserved for MSNA or H⁺ orH₂PO₄ concentrations,suggesting that blood flow was necessary for the expression of thecycle-related effect. The present studies suggest that, during statichandgrip exercise, MSNA is increased during the menstrual compared withthe follicular phase of the ovarian cycle.

     

Ventilatory stability to transient CO2 disturbances in hyperoxia and normoxia in awake humans

Lai, Jie, and Eugene N. Bruce. Ventilatory stability totransient CO₂ disturbances inhyperoxia and normoxia in awake humans. J. Appl.Physiol. 83(2): 466-476, 1997.Modarreszadeh andBruce (J. Appl. Physiol. 76:2765-2775, 1994) proposed that continuous random disturbances inarterial PCO₂ are more likely toelicit ventilatory oscillation patterns that mimic periodic breathingin normoxia than in hyperoxia. To test this hypothesis experimentally,in nine awake humans we applied pseudorandom binary inspiredCO₂ fraction stimulation innormoxia and hyperoxia to derive the closed-loop and open-loopventilatory responses to a briefCO₂ disturbance in terms ofimpulse responses and transfer functions. The closed-loop impulseresponse has a significantly higher peak value [0.143 ± 0.071 vs. 0.079 ± 0.034 (SD)l · min¹ · 0.01 lCO₂¹,P = 0.014] and a significantlyshorter 50% response duration (42.7 ± 13.3 vs. 72.3 ± 27.6 s,P = 0.020) in normoxia than in hyperoxia. Therefore, the ventilatory responses to transientCO₂ disturbances are less damped(but generally not oscillatory) in normoxia than in hyperoxia. For theclosed-loop transfer function, the gain in normoxia increasedsignificantly (P < 0.0005), while phase delay decreased significantly (P < 0.0005). The gain increased by 108.5, 186.0, and 240.6%, whilephase delay decreased by 26.0, 18.1, and 17.3%, at 0.01, 0.03, and0.05 Hz, respectively. Changes in the same direction were found for theopen-loop system. Generally, an oscillatory ventilatory response to asmall transient CO₂ disturbance isunlikely during wakefulness. However, changes in parameters that leadto additional increases in chemoreflex loop gain are more likely toinitiate oscillations in normoxia than in hyperoxia.

     

Development of ventilatory responsiveness to progressive hypoxia and hypercapnia in low-birth-weight lambs

Moss, T. J., M. G. Davey, G. J. McCrabb, and R. Harding.Development of ventilatory responsiveness to progressive hypoxia and hypercapnia in low-birth-weight lambs. J. Appl.Physiol. 81(4): 1555-1561, 1996.Our aim was todetermine the effects of low birth weight on ventilatory responses toprogressive hypoxia and hypercapnia during early postnatal life. Sevenlow-birth-weight (2.7 ± 0.3 kg) and five normal-birth-weight (4.8 ± 0.2 kg) lambs, all born at term, underwent weekly rebreathingtests during wakefulness while arterialPO₂,PCO₂, and pH were measured. Hypoxicventilatory responsiveness (HOVR; percent increase in ventilation whenarterial PO₂ fell to 60% of resting values) increased in normal lambs from 86.6 ± 7.1% atweek 1 to 227.4 ± 24.9% atweek 6. In low-birth-weight lambs,HOVR was not significantly different at week1 (60.1 ± 18.7%) from that of normal lambs but didnot increase with postnatal age (56.6 ± 19.3% atweek 6). HOVR of all lambs at 6 wkwas significantly correlated with birth weight(r² = 0.8).Hypercapnic ventilatory responsiveness (gradient of ventilation vs.arterial PCO₂) did not change withage and was not significantly different between groups [84.7 ± 7.5 (low-birth-weight lambs) vs. 89.4 ± 6.6 ml ^· min^{1 ·} kg^{1 ·} mmHg¹(normal lambs)]. We conclude that intrauterine conditions that impair fetal growth lead to the failure of HOVR to increase with age.

     

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.

     

Ventilation distribution during histamine provocation

Verbanck, S., D. Schuermans, A. Van Muylem, M. Paiva, M. Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J. Appl. Physiol. 83(6):1907-1916, 1997.We investigated ventilation inhomogeneity duringprovocation with inhaled histamine in 20 asymptomatic nonsmokingsubjects. We used N₂multiple-breath washout (MBW) to deriveparameters S_condand S_acin as ameasurement of ventilation inhomogeneity in conductive and acinar zonesof the lungs, respectively. A 20% decrease of forced expiratory volume in 1 s (FEV₁) was used todistinguish responders from nonresponders. In the responder group,average FEV₁ decreased by 26%,whereas S_condincreased by 390% with no significant change inS_acin. In thenonresponder group, FEV₁ decreasedby 11%, whereasS_cond increased by 198% with no significantS_acin change.Despite the absence of change inS_acin duringprovocation, baselineS_acin wassignificantly larger in the responder vs. the nonresponder group. Themain findings of our study are that during provocation largeventilation inhomogeneities occur, that the small airways affected bythe provocation process are situated proximal to the acinar zone wherethe diffusion front stands, and that, in addition to overall decreasein airway caliber, there is inhomogeneous narrowing of parallelairways.