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.

     

Cerebral vasomotor reactivity at high altitude in humans

The purpose of this study was twofold:1) to determine whether at highaltitude cerebral blood flow (CBF) as assessed during CO₂ inhalation and duringhyperventilation in subjects with acute mountain sickness (AMS) wasdifferent from that in subjects without AMS and2) to compare the CBF as assessedunder similar conditions in Sherpas at high altitude and in subjects atsea level. Resting control values of blood flow velocity in themiddle cerebral artery (V_MCA), pulseoxygen saturation (Sa_O2), andtranscutaneous PCO₂ were measured at4,243 m in 43 subjects without AMS, 17 subjects with AMS, 20 Sherpas,and 13 subjects at sea level. Responses ofCO₂ inhalation andhyperventilation onV_MCA,Sa_O2, and transcutaneous PCO₂ were measured, and the cerebralvasomotor reactivity (VMR = V_MCA/PCO₂)was calculated as the fractional change ofV_MCA per Torrchange of PCO₂, yielding ahypercapnic VMR and a hypocapnic VMR. AMS subjects showeda significantly higher resting controlV_MCA than didno-AMS subjects (74 ± 22 and 56 ± 14 cm/s, respectively;P < 0.001), andSa_O2 was significantly lower (80 ± 8 and 88 ± 3%, respectively; P < 0.001). Resting control V_MCA values inthe sea-level group (60 ± 15 cm/s), in the no-AMS group, and inSherpas (59 ± 13 cm/s) were not different. Hypercapnic VMR valuesin AMS subjects were 4.0 ± 4.4, in no-AMS subjects were 5.5 ± 4.3, in Sherpas were 5.6 ± 4.1, and in sea-level subjects were 5.6 ± 2.5 (not significant). Hypocapnic VMR values were significantly higher in AMS subjects (5.9 ± 1.5) compared with no-AMS subjects (4.8 ± 1.4; P < 0.005) but werenot significantly different between Sherpas (3.8 ± 1.1) and thesea-level group (2.8 ± 0.7). We conclude that AMS subjects havegreater cerebral hemodynamic responses to hyperventilation, higherV_MCAresting control values, and lower Sa_O2 compared with no-AMSsubjects. Sherpas showed a cerebral hemodynamic patternsimilar to that of normal subjects at sea level.     

Recovery from mild hypothermia can be accelerated by mechanically distending blood vessels in the hand

Peripheral vasoconstriction decreases thermalconductance of hypothermic individuals, making it difficult to transferexternally applied heat to the body core. We hypothesizedthat increasing blood flow to the skin of a hypothermic individualwould enhance the transfer of exogenous heat to the body core, therebyincreasing the rate of rewarming. External auditory meatus temperature(T_EAM) was monitored inhypothermic subjects during recovery from general anesthesia. In 10 subjects, heat (45-46°C, water-perfused blanket) was appliedto a single forearm and hand that had been placed in a subatmosphericpressure environment (30 to 40 mmHg) to distend the bloodvessels. Heat alone was applied to control subjects (n = 6). The application ofsubatmospheric pressure resulted in a 10-fold increase in rewarmingrates as determined by changes inT_EAM [13.6 ± 2.1 (SE)°C/h in the experimental group vs. 1.4 ± 0.1°C/h in thecontrol group; P < 0.001]. Inthe experimental subjects, the rate of change ofT_EAM decreased sharply asT_EAM neared the normothermic range.

     

Effects of changes in pH and CO2 on pulmonary arterial wall tension are not endothelium dependent

We examined thechanges in isolated pulmonary artery (PA) wall tension on switchingfrom control conditions (pH 7.38 ± 0.01, PCO₂ 32.9 ± 0.4 Torr) toisohydric hypercapnia (pH change 0.00 ± 0.01, PCO₂ change 24.9 ± 1.1 Torr) ornormocapnic acidosis (pH change 0.28 ± 0.01, PCO₂ change 0.3 ± 0.04 Torr) and the role of the endothelium in these responses. In rat PA, submaximally contracted with phenylephrine, isohydric hypercapnia did not cause a significant change in mean (± SE) tension [3.0 ± 1.8% maximal phenylephrine-induced tension(P_o)]. Endothelial removal did not alter this response. In aorticpreparations, isohydric hypercapnia caused significant(P < 0.01) relaxation (27.4 ± 3.2% P_o), which waslargely endothelium dependent. Normocapnic acidosis caused relaxationof PA (20.2 ± 2.6% P_o), which was less(P < 0.01) than that observed in aorticpreparations (35.7 ± 3.4%P_o). Endothelial removal leftthe pulmonary response unchanged while increasing(P < 0.01) the aortic relaxation(53.1 ± 4.4% P_o).These data show that isohydric hypercapnia does not alter PA tone.Reduction of PA tone in normocapnic acidosis is endothelium independentand substantially less than that of systemic vessels.

     

Lactate efflux from exercising human skeletal muscle: role of intracellular PO2

It remainscontroversial whether lactate formation during progressive dynamicexercise from submaximal to maximal effort is due to muscle hypoxia. Tostudy this question, we used direct measures of arterial and femoralvenous lactate concentration, a thermodilution blood flow technique,phosphorus magnetic resonance spectroscopy (MRS), and myoglobin (Mb)saturation measured by ¹H nuclearMRS in six trained subjects performing single-leg quadriceps exercise.We calculated net lactate efflux from the muscle and intracellularPO₂ with subjects breathing room airand 12% O₂. Data were obtained at50, 75, 90, and 100% of quadriceps maximalO₂ consumption at each fraction ofinspired O₂. Mb saturation wassignificantly lower in hypoxia than in normoxia [40 ± 3 vs. 49 ± 3% (SE)] throughout incremental exercise to maximalwork rate. With the assumption of aPO₂ at which 50% of Mb-binding sitesare bound with O₂ of 3.2 Torr,Mb-associated PO₂ averaged 3.1 ± 0.3 and 2.3 ± 0.2 Torr in normoxia and hypoxia, respectively. Netblood lactate efflux was unrelated to intracellular PO₂ across the range of incrementalexercise to maximum (r = 0.03 and 0.07 in normoxia and hypoxia, respectively) but linearly related toO₂ consumption(r = 0.97 and 0.99 in normoxia andhypoxia, respectively) with a greater slope in 12%O₂. Net lactate efflux was alsolinearly related to intracellular pH(r = 0.94 and 0.98 in normoxia andhypoxia, respectively). These data suggest that with increasing workrate, at a given fraction of inspiredO₂, lactate efflux is unrelated tomuscle cytoplasmic PO₂, yet theefflux is higher in hypoxia. Catecholamine values from comparablestudies are included and indicate that lactate efflux in hypoxia may bedue to systemic rather than intracellular hypoxia.

     

Dopamine, sensory discharge, and stimulus interaction with CO2 and O2 in cat carotid body

It is hypothesized that carotid bodychemosensory activity is coupled to neurosecretion. The purpose of thisstudy was to examine whether there was a correspondence between carotidbody tissue dopamine (DA) levels and neuronal discharge (ND) measured from the carotid sinus nerve of perfused cat carotid bodies and tocharacterize interaction betweenCO₂ andO₂ in these responses. ND andtissue DA were measured after changing from normoxic, normocapnic control bicarbonate buffer (PO₂>120 Torr, PCO₂ 25-30 Torr, pH ~ 7.4) to normoxic hypercapnia(PCO₂ 55-57 Torr, pH7.1-7.2) or to hypoxic solutions(PO₂ 30-35 Torr) withnormocapnia (PCO₂ 25-30 Torr, pH ~ 7.4) or hypocapnia (PCO₂10-15 Torr, pH 7.6-7.8). Similar temporal changes for ND and tissue DA were found for all of the stimuli, although there was a much different proportional relationship fornormoxic hypercapnia. Both ND and DA increased above baseline valuesduring flow interruption and normocapnic hypoxia, and both decreasedbelow baseline values during hypoxic hypocapnia. In contrast, normoxichypercapnia caused an initial increase in ND, from a baseline of 175 ± 12 (SE) to a peak of 593 ± 20 impulses/s within 4.6 ± 0.9 s, followed by adaptation, whereas ND declined to 423 ± 20 impulses/s after 1 min. Tissue DA initially increased from a baselineof 17.9 ± 1.2 µM to a peak of 23.2 ± 1.2 µM within 3.0 ± 0.7 s, then declined to 2.6 ± 1.0 µM. The substantialdecrease in tissue DA during normoxic hypercapnia was not consistentwith the parallel changes in DA with ND that were observed for hypoxic stimuli.

     

Catecholaminergic modulation of respiratory rhythm in an in vitro turtle brain stem preparation

An in vitro brainstem preparation from adult turtles was used to determine effects ofdopamine (DA) and norepinephrine (NE) on the pattern of respiratorymotor output recorded from hypoglossal nerve roots (XII). Bath-appliedDA (10-200 µM) increased the frequency of respiratory bursts(peaks) from 0.9 ± 0.2 to 2.4 ± 0.3 (SE) peaks/min, resultingin a 99 ± 9% increase in neural minute activity. R[+]-SCH-23390 (10 µM,D₁ antagonist) and eticlopride (20 µM, D₂ antagonist) attenuatedthe DA-mediated increase in peak frequency by 52 and 59%,respectively. On the other hand, the DA-receptor agonists apomorphine(D₁,D₂), quinelorane(D₂), and SKF-38393 (D₁) had no effect on peakfrequency. Prazosin, an₁-adrenergic antagonist (250 nM) abolished the DA-mediated frequency increase. Although NE(10-200 µM) and phenylephrine (10-200 µM,₁-adrenergic agonist) increasedpeak frequency from 0.5 ± 0.1 to 1.2 ± 0.3 peaks/min and from0.6 ± 0.1 to 1.0 ± 0.2 peaks/min, respectively, these effectswere not as large as that with DA alone. The data suggest that bothdopaminergic and adrenergic receptor activation in the brain stemincrease respiratory frequency in turtles, but the DA receptor-mediatedincrease is dependent on coactivation of₁-adrenergic receptors.

     

Effects of prior exercise on exercise-induced arterial hypoxemia in young women

Twenty-eighthealthy women (ages 27.2 ± 6.4 yr) with widely varying fitnesslevels [maximal O₂consumption (O_{2 max}),31-70 ml · kg¹ · min¹]first completed a progressive incremental treadmill test to O_{2 max} (totalduration, 13.3 ± 1.4 min; 97 ± 37 s at maximal workload), rested for 20 min, and then completed a constant-load treadmill test at maximal workload (total duration, 143 ± 31 s). Atthe termination of the progressive test, 6 subjects had maintained arterial PO₂(Pa_O2) near resting levels, whereas 22 subjects showed a >10 Torr decrease inPa_O2 [78.0 ± 7.2 Torr, arterial O₂ saturation(Sa_O2), 91.6 ± 2.4%], andalveolar-arterial O₂ difference (A-aD_O2,39.2 ± 7.4 Torr). During the subsequent constant-load test, allsubjects, regardless of their degree of exercise-induced arterialhypoxemia (EIAH) during the progressive test, showed a nearly identicaleffect of a narrowed A-aD_O2(4.8 ± 3.8 Torr) and an increase inPa_O2 (+5.9 ± 4.3 Torr) andSa_O2 (+1.6 ± 1.7%) compared with atthe end point of the progressive test. Therefore, EIAH during maximalexercise was lessened, not enhanced, by prior exercise, consistent withthe hypothesis that EIAH is not caused by a mechanismwhich persists after the initial exercise period and is aggravated bysubsequent exercise, as might be expected of exercise-inducedstructural alterations at the alveolar-capillary interface. Rather,these findings in habitually active young women point to a functionallybased mechanism for EIAH that is present only during the exerciseperiod.

     

Blood flow vs. venous pressure effects on filtration coefficient in oleic acid-injured lung

On the basis ofchanges in capillary filtration coefficient(K_fc) in 24 rabbit lungs, we determined whether elevations in pulmonary venouspressure (Ppv) or blood flow (BF) produced differences infiltration surface area in oleic acid-injured (OA) or control (Con)lungs. Lungs were cyclically ventilated and perfused under zone 3 conditions by using blood and 5% albumin with no pharmacological modulation of vascular tone. Pulmonary arterial, venous, and capillary pressures were measured by using arterial, venous, and double occlusion. Before and during eachK_fc-measurementmaneuver, microvascular/total vascular compliance was measured by usingvenous occlusion.K_fc was measuredbefore and 30 min after injury, by using a Ppv elevation of 7 cmH₂O or a BF elevation from 1 to2 l · min¹ · 100 g¹ to obtain a similardouble occlusion pressure. Pulmonary arterial pressure increased morewith BF than with Ppv in both Con and OA lungs [29 ± 2 vs. 19 ± 0.7 (means ± SE) cmH₂O;P < 0.001]. In OA lungscompared with Con lungs, values ofK_fc (200 ± 40 vs. 83 ± 14%, respectively; P < 0.01) and microvascular/total vascular compliance ratio (86 ± 4 vs. 68 ± 5%, respectively; P < 0.01) increased more with BF than with Ppv. In conclusion, for a given OA-induced increase in hydraulic conductivity, BF elevation increased filtration surface area more than did Ppv elevation. The steep pulmonary pressure profile induced by increased BF could result in therecruitment of injured capillaries and could also shift downstream thecompression point of blind (zone 1) and open injured vessels (zone 2).

     

Body composition by air-displacement plethysmography by using predicted and measured thoracic gas volumes

The BOD POD, anew air-displacement plethysmograph for measuring human bodycomposition, utilizes the inverse relationship between pressure andvolume (Boyle's law) to measure body volume directly. The quantity ofair in the lungs during tidal breathing, the average thoracic gasvolume (Vtg), is also measured by the BOD POD by using a standardplethysmographic technique. Alternatively, the BOD POD provides the useof a predicted Vtg (Vtg_pred).The validity of using Vtg_pred inplace of measured Vtg (Vtg_meas)to determine the percentage of body fat (%BF) was evaluated in 50 subjects (36 women, 14 men; ages 18-56 yr). There wasno significant difference betweenVtg_meas andVtg_pred (mean difference ± SE, 53.5 ± 63.3 ml) nor in %BF by usingVtg_meas vs.Vtg_pred (0.2 ± 0.2 %BF). Onan individual basis, %BF measured by usingVtg_meas vs.Vtg_pred differed within ±2.0%BF for 82% of the subjects; maximum differences were 2.9 to+3.0% BF. For comparison, data from 24 subjects who had undergonehydrostatic weighing were evaluated for the validity of using predictedvs. measured residual lung volume(VR_pred vs.VR_meas,respectively). Differences between VR_meas andVR_pred andin %BF calculated by usingVR_meas vs.VR_pred weresignificant (187 ± 46 ml and 1.4 ± 0.3% BF, respectively; P < 0.001). On an individual basis,%BF determined by usingVR_meas vs.VR_preddiffered within ±2.0% BF for 46% of the subjects; maximum differences were 2.9 to +3.8% BF. With respect to %BF measured by air displacement, our findings support the use ofVtg_pred for group mean comparisonsand for purposes such as screening in young to middle-aged individuals.This contrasts with the use ofVR_pred inhydrostatic weighing, which leads to significant errors in theestimation of %BF. Furthermore, although the use ofVtg_pred has some application,determining Vtg_meas is relativelysimple in most cases. Therefore, we recommend that the use ofVtg_meas remain as standardexperimental and clinical practice.

     

Alveolar PCO2 and PO2 of high-altitude natives living at sea level

León-Velarde, Fabiola, Manuel Vargas, Carlos Monge-C.,Robert W. Torrance, and Peter A. Robbins. AlveolarPCO₂ andPO₂ of high-altitude natives livingat sea level. J. Appl.Physiol. 81(4): 1605-1609, 1996.Thisstudy was designed to determine whether subjects born at high altitude(HA; 2,000 m or above) who subsequently move to near sea level (SL)develop end-tidal PCO₂(PET_CO2) andPO₂(PET_O2) valuesthat equal those of SL natives living near SL. A total of 108 male HAnatives living near SL were identified by survey of a district in Lima,Peru, and a further 108 male SL natives from the same district wereidentified as control subjects. Of these subjects, satisfactory datafor inclusion in the study were obtained from 93 HA and 82 SL subjects.Mean PET_CO2 and PET_O2 values were 37.7 ± 2.5 (SD) and 104.7 ± 3.2 Torr, respectively, in HA subjects and37.7 ± 2.2 and 104.8 ± 3.0 Torr, respectively, in SL subjects.The average difference between SL natives and HA natives forPET_CO2 was 0.07 Torr(0.64 to 0.78; 95% confidence interval) and forPET_O2 was 0.05 Torr(0.89 to 0.99, 95% confidence interval). The average age andweight of the SL and HA subjects did not differ, but the HA subjectswere shorter and tended to have larger vital capacities, consistentwith their origin at HA. We conclude that thePET_CO2 andPET_O2 near SL of SL nativesand HA natives do not differ.

     

Hypohydration effects on skeletal muscle performance and metabolism: a 31P-MRS study

The purpose of this study was to determinewhether hypohydration reduces skeletal muscle endurance and whetherincreased H⁺ andP_i might contribute to performancedegradation. Ten physically active volunteers (age 21-40 yr)performed supine single-leg, knee-extension exercise to exhaustion in a1.5-T whole body magnetic resonance spectroscopy (MRS) system wheneuhydrated and when hypohydrated (4% body wt).³¹P spectra were collected at arate of one per second at rest, exercise, and recovery, and weregrouped and averaged to represent 10-s intervals. The desired hydrationlevel was achieved by having the subjects perform 2-3 h ofexercise in a warm room (40°C dry bulb, 20% relative humidity)with or without fluid replacement 3-8 h before the experiment.Time to fatigue was reduced (P < 0.05) by 15% when the subjects were hypohydrated [213 ± 12 vs. 251 ± 15 (SE) s]. Muscle strength was generally notaffected by hypohydration. Muscle pH andP_i/-ATP ratio were similarduring exercise and at exhaustion, regardless of hydration state. The time constants for phosphocreatine recovery were also similar betweentrials. In summary, moderate hypohydration reduces muscle endurance,and neither H⁺ norP_i concentration appears to berelated to these reductions.

     

Two-photon molecular excitation imaging of Ca2+ transients in Langendorff-perfused mouse hearts

The ability to image calciumsignals at subcellular levels within the intact depolarizing heartcould provide valuable information toward a more integratedunderstanding of cardiac function. Accordingly, a system combiningtwo-photon excitation with laser-scanning microscopy was developed tomonitor electrically evoked [Ca²⁺]_itransients in individual cardiomyocytes within noncontracting Langendorff-perfused mouse hearts. [Ca²⁺]_itransients were recorded at depths 100 µm from the epicardial surface with the fluorescent indicators rhod-2 or fura-2 in the presence of the excitation-contraction uncoupler cytochalasin D. Evoked[Ca²⁺]_i transients were highly synchronizedamong neighboring cardiomyocytes. At 1 Hz, the times from 90 to 50%(t_90-50%) and from 50 to 10%(t_50-10%) of the peak[Ca²⁺]_i were (means ± SE) 73 ± 4 and 126 ± 10 ms, respectively, and at 2 Hz, 62 ± 3 and94 ± 6 ms (n = 19, P < 0.05 vs.1 Hz) in rhod-2-loaded cardiomyocytes.[Ca²⁺]_i decay was markedly slower infura-2-loaded hearts (t_90-50% at 1 Hz,128 ± 9 ms and at 2 Hz, 88 ± 5 ms;t_50-10% at 1 Hz, 214 ± 18 ms and at2 Hz, 163 ± 7 ms; n = 19, P < 0.05 vs. rhod-2). Fura-2-induced deceleration of[Ca²⁺]_i decline resulted from increasedcytosolic Ca²⁺ buffering, because the kinetics of rhod-2decay resembled those obtained with fura-2 after incorporation of theCa²⁺ chelator BAPTA. Propagating calcium waves and[Ca²⁺]_i amplitude alternans were readilydetected in paced hearts. This approach should be of general utility tomonitor the consequences of genetic and/or functional heterogeneity incellular calcium signaling within whole mouse hearts at tissue depthsthat have been inaccessible to single-photon imaging.

     

Differences between estimates and measured PaCO2 during rest and exercise in older subjects

Williams, J. S., and T. G. Babb. Differences betweenestimates and measured Pa_CO2 during restand exercise in older subjects. J. Appl.Physiol. 83(1): 312-316, 1997.ArterialPCO₂ (Pa_CO2) has been estimated duringexercise with good accuracy in younger individuals by using the Jonesequation(P_JCO₂)(J. Appl. Physiol. 47: 954-960,1979). The purpose of this project was to determine the utility ofestimating Pa_CO2 from end-tidal PCO₂(PET_CO2) orP_JCO₂at rest, ventilatory threshold (Th), and maximalexercise (Max) in older subjects. PET_CO2 was determined fromrespired gases simultaneously (MGA 1100) with arterial blood gases(radial arterial catheter) in 12 older and 11 younger subjects at restand during exercise. Mean differences were analyzed with pairedt-tests, and relationships between theestimated Pa_CO2 values and the actualvalues of Pa_CO2 were determined withcorrelation coefficients. In the older subjects, PET_CO2 was not significantlydifferent from Pa_CO2 at rest (1.2 ± 4.3 Torr), Th (0.4 ± 2.5), or Max(0.8 ± 2.7), and the two were significantly(P < 0.05) correlated atth (r = 0.84) andMax (r = 0.87) but not atrest (r = 0.47).P_JCO₂was similar to Pa_CO2 at rest (1.0 ± 3.9) and th (1.3 ± 2.3) but significantly lower at Max (3.0 ± 2.6), and the two weresignificantly correlated at th(r = 0.86) and Max(r = 0.80) but not at rest (r = 0.54).PET_CO2 was significantlyhigher than Pa_CO2 during exercise in theyounger subjects but similar to Pa_CO2 at rest.P_JCO₂was similar to Pa_CO2 at rest andth but significantly lower at Max in youngersubjects. In conclusion, our data demonstrate thatPa_CO2 during exercise is betterestimated by PET_CO2 than byP_JCO₂in older subjects, contrary to what is observed in younger subjects.This appears to be related to the finding thatPET_CO2 does not exceedPa_CO2 during exercise in older subjects,as occurs in the younger subjects. However,Pa_CO2 at rest is best estimated byP_JCO₂in both younger and older subjects.

     

Nonchemical influence of inspiratory pressure support on inspiratory activity in humans

To determinewhether nonchemical inhibition of respiratory activity occurs duringinspiratory pressure support (IPS) ventilation (IPSV), respiratorymotor output (in 9 subjects), obtained by calculatingtransdiaphragmatic pressure-time products, and central respiratoryoutput (in 5 subjects), obtained by integrating the electromyographicactivity of the diaphragm (EMGdi) during mechanical inspiratory time,EMGdi per minute, and electrical inspiratory time, asdetermined from onset to peak EMGdi, were compared during spontaneous ventilation (control) and IPSV with(IPS+CO₂) and without (IPS)correction of hypocapnia. Both IPS andIPS+CO₂ induced significantdecreases in transdiaphragmatic pressure-time products (46 ± 31 and53 ± 23%, respectively), EMGdi during mechanical inspiratory time(49 ± 12 and 57 ± 14%, respectively), EMGdi per minute (65 ± 22 and 69 ± 15%, respectively), andelectrical inspiratory time (73 ± 8 and 65 ± 6%,respectively). Because correction of hypocapnia failed to eliminate themarked inhibition of both respiratory and central motor output seenwith IPS, we conclude that nonchemical inhibition of respiratoryactivity occurs during IPSV.

     

Phosphocreatine hydrolysis during submaximal exercise: the effect of FIO2

There isevidence that the concentration of the high-energy phosphatemetabolites may be altered during steady-state submaximal exerciseby the breathing of different fractions of inspiredO₂ (FI_O2). Whereasit has been suggested that these changes may be the result ofdifferences in time taken to achieve steady-state O₂ uptake(O₂) at differentFI_O2 values, we postulated that they are due to a direct effect ofO₂ tension. We used³¹P-magnetic resonancespectroscopy during constant-load, steady-state submaximal exercise todetermine 1) whether changes inhigh-energy phosphates do occur at the sameO₂ with variedFI_O2 and2) that these changes are not due todifferences in O₂onset kinetics. Six male subjects performed steady-state submaximal plantar flexion exercise [7.2 ± 0.6 (SE) W] for 10 minwhile lying supine in a 1.5-T clinical scanner. Magnetic resonancespectroscopy data were collected continuously for 2 min beforeexercise, 10 min during exercise, and 6 min during recovery. Subjectsperformed three different exercise bouts at constant load with theFI_O2 switched after 5 min ofthe 10-min exercise bout. The three exercise treatments were1)FI_O2 of 0.1 switched to0.21, 2)FI_O2 of 0.1 switched to1.00, and 3)FI_O2 of 1.00 switched to0.1. For all three treatments, theFI_O2 switch significantly (P  0.05) altered phosphocreatine:1) 55.5 ± 4.8 to 67.8 ± 4.9% (%rest); 2) 59.0 ± 4.3 to72.3 ± 5.1%; and 3) 72.6 ± 3.1 to 64.2 ± 3.4%, respectively. There were no significantdifferences in intracellular pH for the three treatments. The resultsdemonstrate that the differences in phosphocreatine concentration withvaried FI_O2 are not theresult of different O₂onset kinetics, as this was eliminated by the experimental design.These data also demonstrate that changes in intracellular oxygenation,at the same work intensity, result in significant changes in cell homeostasis and thereby suggest a role for metabolic control by O₂ even during submaximalexercise.

     

Within-night variation in respiratory effort preceding apnea termination and EEG delta power in sleep apnea

We studied the within-night variability of themaximum esophageal pressure deflection before apnea termination(DP_max) in nine patients withsevere obstructive sleep apnea as an index of the arousal threshold andthe mean electroencephalogram (EEG) delta power for each 30 s as anindex of the timing of sleep cycles. Periodicity in the time variationof delta power and DP_max was analyzed by determining their power spectral density and their relationship determined by cross correlation.DP_max and delta power variedcyclically and in phase with a major periodicity (major peak in powerspectral density) of 117.6 ± 8.8 (SE) min. The correlation betweenthe values of DP_max and deltapower was significant (P < 0.001) ineach subject (mean r = 0.47 ± 0.03), and the coherence betweenDP_max and delta power at theirdominant frequency was high. Within cycles of non-rapid-eye-movementsleep, DP_max and delta powerincreased, reaching peak values on average at or after midcycle. Thesefindings suggest that the arousal threshold to airway occlusion inpatients with obstructive sleep apnea varies cyclically during thenight synchronous to the underlying cycles of sleep.

     

Esophageal temperature threshold for sweating decreases before ovulation in premenopausal women

The purpose ofthis study was to test the hypothesis that regulated body temperatureis decreased in the preovulatory phase in eumenorrheic women. Six womenwere studied in both the preovulatory phase (Preov-2;days 9-12), which was 1-2days before predicted ovulation when 17-estradiol(E₂) was estimated to peak, andin the follicular phase (F; days2-6). The subjects walked on a treadmill (~225W · m²)in a warm chamber (ambient temperature = 30°C; dew-pointtemperature = 11.5°C) while heavily clothed.E₂, esophageal temperature(T_es), local skin temperatures,and local sweating rate were measured. The estimate of when theE₂ surge would occur was correctfor four of six subjects. In these four subjects,E₂ increased(P  0.05) from 42.0 ± 24.5 pg/mlduring F to 123.2 ± 31.3 pg/ml during Preov-2. RestingT_es was 37.02 ± 0.20°Cduring F and 36.76 ± 0.28°C during Preov-2(P  0.05). TheT_es threshold for sweating wasdecreased (P  0.05) from 36.88 ± 0.27°C during F to 36.64 ± 0.35°C during Preov-2. Both meanskin and mean body temperatures were decreased during rest in Preov-2group. The hypothesis that regulated body temperature is decreasedduring the preovulatory phase is supported.

     

Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E.coli pneumonia and sepsis

Quezado, Zenaide M. N., Charles Natanson, WaheedullahKarzai, Robert L. Danner, Cezar A. Koev, Yvonne Fitz, Donald P. Dolan, Steven Richmond, Steven M. Banks, Laura Wilson, and Peter Q. Eichacker. Cardiopulmonary effects of inhaled nitric oxide in normal dogs andduring E. coli pneumonia and sepsis.J. Appl. Physiol. 84(1): 107-115, 1998.We investigated the effect of inhaled nitric oxide (NO) atincreasing fractional inspired O₂concentrations (FI_O2) onhemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious,spontaneously breathing, tracheotomized 2-yr-old beagles hadintrabronchial inoculation with either 0.75 or 1.5 × 10¹⁰ colony-forming units/kg ofE. coli 0111:B4(infected) or 0.9% saline (noninfected) in one or four pulmonarylobes. We found that neither the severity nor distribution (lobar vs.diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasingFI_O2 (0.08, 0.21, 0.50, and0.85), NO (80 parts/million) progressively increased arterial PO₂ [0.3 ± 0.6, 3 ± 1, 13 ± 4, 10 ± 9 (mean ± SE) Torr, respectively] and decreased the mean arterial-alveolarO₂ gradient (0.5 ± 0.3, 4 ± 2, 8 ± 7, 10 ± 9 Torr, respectively). Incontrast, in noninfected animals, the effect of NO was significantlydifferent and opposite; NO progressively decreased meanPO₂ with increasingFI_O2 (2 ± 1, 5 ± 3, 2 ± 3, and 12 ± 5 Torr, respectively;P < 0.05 compared with infectedanimals) and increased mean arterial-alveolarO₂ gradient (0.3 ± 0.04, 2 ± 2, 1 ± 3, 11 ± 5 Torr; P < 0.05 compared with infected animals). In normal and infectedanimals alike, only at FI_O20.21 did NO significantly lower mean pulmonary artery pressure,pulmonary artery occlusion pressure, and pulmonary vascular resistanceindex (all P < 0.01).However, inhaled NO had no significant effect on increases in meanpulmonay artery pressure associated with bacterial pneumonia. Thus,during bacterial pneumonia, inhaled NO had only modest effects onoxygenation dependent on highFI_O2 and did not affectsepsis-induced pulmonary hypertension. These data do not support a rolefor inhaled NO in bacterial pneumonia. Further studies are necessary todetermine whether, in combination with ventilatory support, NO may havemore pronounced effects.

     

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.