MRI study of regional variations of pharyngeal wall compliance in cats

Upper airway compliance indicates the potentialof the airway to collapse and is relevant to the pathogenesis ofobstructive sleep apnea. We hypothesized that compliance would varyover the rostral-to-caudal extent of the pharyngeal airway. In aparalyzed isolated upper airway preparation in cats, we controlledstatic upper airway pressure during magnetic resonance imaging (MRI, 0.391-mm resolution). We measured cross-sectional area andanteroposterior and lateral dimensions from three-dimensionalreconstructed MRIs in axial slices orthogonal to the airway centerline.High-retropalatal (HRP), midretropalatal (MRP), and hypopharyngeal(HYP) regions were defined. Regional compliance was significantlyincreased from rostral to caudal regions as follows: HRP < MRP < HYP (P < 0.0001), and compliancedifferences among regions were directly related to collapsibility. Thusour findings in the isolated upper airway of the cat support thehypothesis that regional differences in pharyngeal compliance exist andsuggest that baseline regional variations in compliance andcollapsibility may be an important factor in the pathogenesis andtreatment of obstructive sleep apnea.

     

Respiratory-related pharyngeal constrictor muscle activity in decerebrate cats

Kuna, Samuel T., and Christi R. Vanoye.Respiratory-related pharyngeal constrictor muscle activity indecerebrate cats. J. Appl. Physiol.83(5): 1588-1594, 1997.Respiratory-related activity of thehyopharyngeus (middle pharyngeal constrictor) and thyropharyngeus(inferior pharyngeal constrictor) muscles was determined indecerebrate, tracheotomized adult cats and compared with theelectromyographic activity of the thyroarytenoid, a vocal cordadductor. During quiet breathing, the hyopharyngeus and usually thethyroarytenoid exhibited phasic activity during expiration and tonicactivity throughout the respiratory cycle. Respiratory-related thyropharyngeus activity was absent under these conditions. Progressive hyperoxic hypercapnia and progressive isocapnic hypoxia increased phasic expiratory activity in both pharyngeal constrictor (PC) musclesbut tended to suppress thyroarytenoid activity. Passively inducedhypocapnia and the central apnea that followed the cessation of themechanical hyperventilation were associated with tonic activation ofthe hyopharyngeus and thyroarytenoid but no recruitment inthyropharyngeus activity. The expiratory phase of a sigh and progressive pneumothorax were associated with an increase in phasic thyroarytenoid activity but no change in phasic PC activity. The results indicate that a variety of stimuli modulate respiratory-related PC activity, suggesting that the PC muscles may have a role in theregulation of upper airway patency during respiration.

     

Lateral pharyngeal fat pad pressure during breathing in anesthetized pigs

Winter, W. Christopher, Tom Gampper, Spencer B. Gay, andPaul M. Suratt. Lateral pharyngeal fat pad pressure during breathing in anesthetized pigs. J. Appl.Physiol. 83(3): 688-694, 1997.It has beenhypothesized that the pressure in tissues surrounding the upper airwayis one of the determinants of the size and shape of the upper airway.To our knowledge, this pressure has not been measured. The purpose ofthis study was to test whether the pressure in a tissue lateral to theupper airway, the lateral pharyngeal fat pad pressure (Pfp), differsfrom atmospheric and pharyngeal pressures and whether it changes withbreathing. We studied six male lightly sedated pigs by inserting atransducer tipped catheter into their fat pad space by usingcomputerized tomographic scan guidance. We measured airflow with apneumotachograph attached to a face mask and pharyngeal pressure with aballoon catheter. Pfp differed from atmospheric pressure, generallyexceeding it, and from pharyngeal pressure. Pfp correlated positivelywith airflow and with pharyngeal pressure, decreasing duringinspiration and increasing during expiration. Changes in Pfp withventilation were eliminated by oropharyngeal intubation. We concludethat Pfp differs from atmospheric and pharyngeal pressures and that itchanges with breathing.

     

Elastic moduli of excised constricted rat lungs

When airways constrict, the surrounding parenchyma undergoesstretch and distortion. Because of the mechanical interdependence between airways and parenchyma, the material properties of the parenchyma are important factors that modulate the degree ofbronchoconstriction. The purpose of this study was to investigate theeffect of changes in transpulmonary pressure (Ptp) and inducedconstriction on parenchymal bulk (k)and shear (µ) moduli. In excised rat lungs, pressure was measured atthe airway opening, and pressure-volume curves were obtained byimposing step decreases in volume with a calibrated syringe from totallung inflation. Calculation was made ofk during small-volume oscillations (1 Hz). Absolute lung volume at 0 cmH₂O Ptp was obtained bysaline displacement. To calculate µ, a lung-indentation test wasperformed. The lung surface was deformed with a cylindrical punch(diameter = 0.45 cm) in 0.25-mm increments, and the force required toeffect this displacement was measured by a weight balance. Measurementsof k and µ were obtained at 4 and 10 cmH₂O Ptp, and again at 4 cmH₂O Ptp, after delivery ofmethacholine aerosol (100 mg/ml) into the trachea. Values ofk and µ in rat lungs were similar tothose reported in other species. In addition, k and µ were dependent on Ptp. Afterinduced constriction, k and µ increased significantly. That k and µ can increase after induced constriction has important implicationsvis a vis the factors modulating airway narrowing.

     

Long-term facilitation of upper airway muscle activities in vagotomized and vagally intact cats

Mateika, J. H., and R. F. Fregosi. Long-termfacilitation of upper airway muscle activities in vagotomized andvagally intact cats. J. Appl. Physiol.82(2): 419-425, 1997.The primary purpose of the presentinvestigation was to determine whether long-term facilitation (LTF) ofupper airway muscle activities occurs in vagotomized and vagally intactcats. Tidal volume and diaphragm, genioglossus, and nasal dilatormuscle activities were recorded before, during, and after one carotidsinus nerve was stimulated five times with 2-min trains of constantcurrent. Sixty minutes after stimulation, nasal dilator andgenioglossus muscle activities were significantly greater than controlin the vagotomized cats but not in the vagally intact cats. Tidalvolume recorded from the vagotomized and vagally intact cats wassignificantly greater than control during the poststimulation period.In contrast, diaphragm activities were not significantly elevated inthe poststimulation period in either group of animals. We conclude that1) LTF of genioglossus and nasaldilator muscle activities can be evoked in vagotomized cats;2) vagal mechanisms inhibit LTF inupper airway muscles; and 3) LTF canbe evoked in accessory inspiratory muscles because LTF of inspiredtidal volume was greater than LTF of diaphragm activity.

     

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.

     

Regional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume

The regionaldeposition of particles in boluses delivered to shallow lung depths andtheir subsequent retention in the airways may depend on the lung volumeat which the boluses are delivered. To evaluate the effectof end-inspiratory lung volume on aerosol bolus delivery, we hadhealthy subjects inhale radiolabeled, monodisperse aerosol(^99mTc-iron oxide, 3.5-µm massmedian aerodynamic diameter) boluses (40 ml) to a volumetric frontdepth of 70 ml into the lung at lung volumes of 50, 70, and 85% oftotal lung capacity (TLC) end inhalation. By gamma camera analysis, wefound significantly greater deposition in the left (L) vs. right (R)lungs at the 70 and 85% TLC end inhalation; ratio of deposition in Lto R lung, normalized to L-to-R ratio of lung volume (mean L/R), was1.60 ± 0.45 (SD) and 1.96 ± 0.72, respectively(P < 0.001 for comparison to 1.0) for posterior images. However, at 50% TLC, L/R was 1.23 ± 0.37, not significantly different from 1.0. These data suggest that the L andR lungs may be expanding nonuniformly at higher lung volumes. On theother hand, subsequent retention of deposited particles at 2 and 24 hpostdeposition was independent of L/R at the various lung volumes. Thusasymmetric bolus ventilation for these very shallow boluses does notlead to significant increases in peripheral alveolar deposition. Thesedata may prove useful for 1)designing aerosol delivery techniques to target bronchial airways and2) understanding airway retention ofinhaled particles.

     

Expanded blood volumes contribute to the increased cardiovascular performance of endurance-trained older men

To determine whether expanded intravascular volumes contributeto the older athlete's higher exercise stroke volume and maximal oxygen consumption(O_{2 max}),we measured peak upright cycle ergometry cardiac volumes(^99mTc ventriculography) andplasma (¹²⁵I-labeled albumin) andred cell (NaCr⁵¹) volumes in 7 endurance-trained and 12 age-matched lean sedentary men. The athleteshad ~40% higherO_{2 max} values thandid the sedentary men and larger relative plasma (46 vs. 38 ml/kg), red cell (30 vs. 26 ml/kg), and total blood volumes (76 vs. 64 ml/kg) (allP < 0.05). Athletes hadlarger peak cycle ergometer exercise stroke volume indexes (75 vs. 57 ml/m²,P < 0.05) and 17% largerend-diastolic volume indexes. In the total group,O_{2 max}correlated with plasma, red cell, and total blood volumes(r = 0.61-0.70,P < 0.01). Peakexercise stroke volume was correlated directly with the blood volumevariables (r = 0.59-0.67,P < 0.01). Multiple regressionanalyses showed that fat-free mass and plasma or total blood volume,but not red cell volume, were independent determinants ofO_{2 max} andpeak exercise stroke volume. Plasma and total blood volumes correlated with the stroke volume and end-diastolic volume changes from rest topeak exercise. This suggests that expanded intravascular volumes, particularly plasma and total blood volumes, contribute to the higherpeak exercise left ventricular end-diastolic volume, stroke volume, andcardiac output and hence the higherO_{2 max} in master athletes by eliciting both chronic volume overload and increased utilization of the Frank-Starling effect during exercise.

     

Effects of temperature on slow and fast inactivation of rat skeletal muscle Na+ channels

Patch-clampstudies of mammalian skeletal muscleNa⁺ channels are commonly done atsubphysiological temperatures, usually room temperature. However, atsubphysiological temperatures, mostNa⁺ channels are inactivated atthe cell resting potential. This study examined the effects oftemperature on fast and slow inactivation ofNa⁺ channels to determine iftemperature changed the fraction of Na⁺ channels that were excitableat resting potential. The loose patch voltage clamp recordedNa⁺ currents(I_Na) in vitroat 19, 25, 31, and 37°C from the sarcolemma of rat type IIbfast-twitch omohyoid skeletal muscle fibers. Temperature affected thefraction of Na⁺ channels that wereexcitable at the resting potential. At 19°C, only 30% of channelswere excitable at the resting potential. In contrast, at 37°C, 93%of Na⁺ channels were excitable atthe resting potential. Temperature did not alter the resting potentialor the voltage dependencies of activation or fast inactivation.I_Na available atthe resting potential increased with temperature because thesteady-state voltage dependence of slow inactivation shifted in adepolarizing direction with increasing temperature. The membranepotential at which half of the Na⁺channels were in the slow inactivated state was shifted by +16 mV at37°C compared with 19°C. Consequently, the low availability ofexcitable Na⁺ channels atsubphysiological temperatures resulted from channels being in the slow,inactivated state at the resting potential.

     

Ventricular activation during sympathetic imbalance and its computational reconstruction

We characterized the epicardialactivation sequence during a norepinephrine (NE)-induced ventriculararrhythmia in anesthetized pigs and studied factors that modulatedit. Subepicardial NE infusion caused the QRS complex to invertwithin a single beat (n = 35 animals, 101 observations), and the earliest epicardial activation consistentlyshifted to the randomly located infusion site (n = 14).This preceded right atrial activation, whereas the total ventricularepicardial activation time increased from 20 ± 4 to 50 ± 9 ms (P < 0.01). These events were accompanied by aventricular tachycardia and a drop in left ventricular pressure, whichwere fully reversed after the infusion was stopped. Epicardial pacing at the infusion site mimicked all electrical and hemodynamic changes induced by NE. The arrhythmia was prevented by propranolol and abolished by cardiac sympathetic or vagal nerve stimulation. Focal automaticity was computationally reconstructed using a two-dimensional sheet of 256 × 256 resistively coupled ventricular cells, where calcium handling was abnormally high in the central region. We concludethat adrenergic stimulation to a small region of the ventricle elicitstriggered automaticity and that computational reconstruction implicatescalcium overload. Interventions that reduce spatial inhomogeneities ofintracellular calcium may prevent this type of arrhythmia.

     

Partitioning of airway and respiratory tissue mechanical impedances by body plethysmography

Peslin, R., and C. Duvivier. Partitioning of airway andrespiratory tissue mechanical impedances by body plethysmography. J. Appl. Physiol. 84(2): 553-561, 1998.We have tested the feasibility of separating the airway (Zaw)and tissue (Zti) components of total respiratory input impedance(Zrs,in) in healthy subjects by measuring alveolar gas compression bybody plethysmography (Vpl) during pressure oscillations at the airwayopening. The forced oscillation setup was placed inside a bodyplethysmograph, and the subjects rebreathedBTPS gas. Zrs,in and the relationship between Vpl and airway flow (Hpl) were measured from 4 to 29 Hz. Zawand Zti were computed from Zrs,in and Hpl by using the monoalveolar T-network model and alveolar gas compliance derived from thoracic gasvolume. The data were in good agreement with previous observations: airway and tissue resistance exhibited some positive and negative frequency dependences, respectively; airway reactance was consistent with an inertance of 0.015 ± 0.003 hPa · s² · l¹and tissue reactance with an elastance of 36 ± 8 hPa/l. The changes seen with varying lung volume, during elastic loading of the chest andduring bronchoconstriction, were mostly in agreement with the expectedeffects. The data, as well as computer simulation, suggest that thepartitioning is unaffected by mechanical inhomogeneity and onlymoderately affected by airway wall shunting.

     

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.

     

Beat-to-beat modulation of heart rate is coupled to coronary perfusion pressure in the isolated heart

A goal ofclinicians caring for heart transplant recipients has been to use heartrate variability as a noninvasive means of diagnosing graftrejection. The determinants of beat-to-beat variability inthe surgically denervated heart have yet to be elucidated. We used anisolated, blood buffer-perfused porcine heart preparation toquantitatively assess the relationship between coronary perfusion andsinus node automaticity. Hearts(n = 9) were suspended in aLangendorff preparation, and heart rate (HR) fluctuations werequantified while perfusion pressure was modulated between 70/50, 80/60,90/70, and 100/80 mmHg at 0.067 Hz. In 32 of 32 recordings, the crossspectrum of perfusion pressure vs. HR showed the largest peak centeredat 0.067 Hz. In eight of nine experiments during nonpulsatileperfusion, HR accelerated as perfusion pressure was increased from 40 to 110 mmHg (mean increase 24.2 ± 3.0 beats/min). HR increased 0.34 beats/min per mmHg increase in perfusion pressure (least squares linearregression y = 25.8 mmHg + 0.34x;r = 0.88, P < 0.0001). Administration of low-and high-dose nitroglycerin (Ntg) resulted in a modest increase in flowbut produced a significant decrease in HR and blunted the response ofHR to changes in perfusion pressure (HR increase 0.26 beats · min¹ · mmHg¹,r = 0.87, P < 0.0001 after low-dose Ntg; 0.25 beats · min¹ · mmHg¹,r = 0.78, P < 0.0001 after high-dose Ntg).These experiments suggest that sinus node discharge in the isolatedperfused heart is mechanically coupled to perfusion pressure on abeat-to-beat basis.     

Voluntary activation of the human diaphragm in health and disease

Intersubjectcomparison of the crural diaphragm electromyogram, as measured by anesophageal electrode, requires a reliable means for normalizing thesignal. The present study set out 1) to evaluate which voluntary respiratory maneuvers provide high andreproducible diaphragm electromyogram root-mean-square (RMS) values and2) to determine the relativediaphragm activation and mechanical and ventilatory outputs duringbreathing at rest in healthy subjects(n = 5), in patients with severechronic obstructive pulmonary disease (COPD,n = 5), and in restrictive patientswith prior polio infection (PPI, n = 6). In all groups, mean voluntary maximal RMS values were higher duringinspiration to total lung capacity than during sniff inhalation throughthe nose (P = 0.035, ANOVA). The RMS(percentage of voluntary maximal RMS) during quiet breathing was 8% inhealthy subjects, 43% in COPD patients, and 45% in PPI patients.Despite the large difference in relative RMS(P = 0.012), there were no differencesin mean transdiaphragmatic pressure (P = 0.977) and tidal volumes (P = 0.426). We conclude that voluntary maximal RMS is reliably obtainedduring an inspiration to total lung capacity but a sniff inhalationcould be a useful complementary maneuver. Severe COPD and PPI patientsbreathing at rest are characterized by increased diaphragm activationwith no change in diaphragm pressure generation.

     

Contractile Proteins of a Benthic Fish. II. Composition and ATPase Properties of Actomyosin

SYNOPSIS. Actomyosin was extracted from skeletal muscle of Coryphaenoides,a benthic fish living at 2,200 meters depth, at a temperatureof 2°C, or less, and at pressure of 3,000 psi. On SDS-ureaelectrophoresis on acrylamide gel, the actomyosin extracts yieldcomponents of apparent molecular weight 210,000 (myosin heavychains), 47,000 (actin), 35,000 (tropomyosin and/or troponinsubunits), and 13,000 (myosin light chains). The Mg²⁺-ATPaseof Coryphaenoides actomyosin shows a complex Arrhenius plot,with marked denaturation at temperatures above 30°C, anddiminished temperature sensitivity at temperatures below 15°C.Mg²⁺-ATPase is inhibited by pressure, with activation volumesof + 160 cc/mole at 25°C, and + 230 cc/mole at 2°C.Ca²⁺-ATPase of actomyosin exhibits the same pH, temperature,and pressure dependence as Ca²⁺-ATPase of myosin. The overalldata would be consistent with a positive activation volume thatis independent of temperature (to first approximation) and isrelated to the interaction of actin and myosin, and a negativeactivation volume that is temperature dependent and is relateddirectly to activation of myosin ATPase. The net effect appearsto be an adaptive mechanism whereby Mg²⁺-ATPase of Coryphaenoidesactomyosin is relatively insensitive to pressure and temperatureunder conditions encountered by the living fish.     

Human respiratory input impedance between 32and 800Hz, measured by interrupter technique and forced oscillations

Frey, Urs, Bela Suki, Richard Kraemer, and Andrew C. Jackson. Human respiratory input impedance between 32 and 800 Hz,measured by interrupter technique and forced oscillations. J. Appl. Physiol. 82(3):1018-1023, 1997.Respiratory input impedance (Zin) over a widerange of frequencies (f) has beenshown to be useful in determining airway resistance (Raw) and tissueresistance in dogs or airway wall properties in human adults. Zinmeasurements are noninvasive and, therefore, potentially useful ininvestigation of airway mechanics in infants. However, accuratemeasurements of Zin at these f valueswith the use of forced oscillatory techniques (FOT) in infants aredifficult because of their relatively high Raw and large compliance ofthe face mask. If pseudorandom noise pressure oscillations generated bya loudspeaker are applied at the airway opening (FOT), the power of theresulting flow decreases inversely withf because of capacitive shunting intothe volume of the gas in the speaker chamber and in the face mask. Westudied whether high-frequency respiratory Zin can be measured by using rapid flow interruption [high-speed interrupter technique(HIT)], in which we expect the flow amplitude in the respiratorysystem to be higher than in the FOT. We compared Zin measured by HIT with Zin measured by FOT in a dried dog lung and in five healthy adultsubjects. The impedance was calculated from two pressure signalsmeasured between the mouth and the HIT valve. The impedance could beassessed from 32 to 800 Hz. Its real part at lowf as well as thef and amplitude of the first andsecond acoustic resonance, measured by FOT and by HIT, were notsignificantly different. The power spectrum of oscillatory flow whenthe HIT was used showed amplitudes that were at least 100 times greaterthan those when FOT was used, increasing atf > 400 Hz. In conclusion,the HIT enables the measurement of high-frequency Zin data ranging from 32 to 800 Hz with particularly high flow amplitudes and, therefore, possibly better signal-to-noise ratio. This is particularly important in systems with high Raw, e.g., in infants, when measurements have tobe performed through a face mask.

     

Inhibition of nitric oxide synthase slows heart rate recovery from cholinergic activation

The role ofnitric oxide (NO) in the cholinergic regulation of heart rate(HR) recovery from an aspect of simulated exercise wasinvestigated in atria isolated from guinea pig to test the hypothesisthat NO may be involved in the cholinergic antagonism of the positivechronotropic response to adrenergic stimulation. Inhibition of NOsynthesis withN^G-monomethyl-L-arginine(L-NMMA, 100 µM) significantlyslowed the time course of the reduction in HR without affecting themagnitude of the response elicited by bath-applied ACh (100 nM) orvagal nerve stimulation (2 Hz). The half-times(t_1/2) of responses were 3.99 ± 0.41 s in control vs. 7.49 ± 0.68 s inL-NMMA(P < 0.05). This was dependent onprior adrenergic stimulation (norepinephrine, 1 µM). The effect ofL-NMMA was reversed byL-arginine (1 mM; t_1/2 4.62 ± 0.39 s). The calcium-channelantagonist nifedipine (0.2 µM) also slowed the kinetics of thereduction in HR caused by vagal nerve stimulation. However, thet_1/2 for the reduction in HR with antagonists (2 mM Cs⁺ and 1 µM ZD-7288) of thehyperpolarization-activated current were significantlyfaster compared with control. There was no additional effect ofL-NMMA orL-NMMA+L-arginineon vagal stimulation in groups treated with nifedipine,Cs⁺, or ZD-7288. Weconclude that NO contributes to the cholinergic antagonism of thepositive cardiac chronotropic effects of adrenergic stimulation byaccelerating the HR response to vagal stimulation. This may involve aninterplay between two pacemaking currents (L-type calcium channelcurrent and hyperpolarization-activated current). Whether NO modulatesthe vagal control of HR recovery from actual exercise remains to bedetermined.

     

Effects of pharyngeal lubrication on the opening of obstructed upper airway.

We examined the effect of electrical stimulation of the hypoglossal nerve and pharyngeal lubrication with artificial surfactant (Surfactant T-A) on the opening of obstructed upper airway in nine anesthetized supine dogs. The upper airway was isolated from the lower airway by transecting the cervical trachea. Upper airway obstruction was induced by applying constant negative pressures (5, 10, 20, and 30 cmH2O) on the rostral cut end of the trachea. Peripheral cut ends of the hypoglossal nerves were electrically stimulated by square-wave pulses at various frequencies from 10 to 30 Hz (0.2-ms duration, 5-7 V), and the critical stimulating frequency necessary for opening the obstructed upper airway was measured at each driving pressure before and after pharyngeal lubrication with artificial surfactant. The critical stimulation frequency for upper airway opening significantly increased as upper airway pressure became more negative and significantly decreased with lubrication of the upper airway. These findings suggest that greater muscle tone of the genioglossus is needed to open the occluded upper airway with larger negative intraluminal pressure and that lubrication of the pharyngeal mucosa with artificial surfactant facilitates reopening of the upper airway.     

Estimation of thickness of airwaysurface liquid in ferret trachea in vitro

Duneclift, S., U. Wells, and J. Widdicombe. Estimationof thickness of airway surface liquid in ferret trachea in vitro. J. Appl. Physiol. 83(3): 761-767, 1997.The tracheae of ferrets and rabbits were mounted in vitro inorgan baths. While the tracheae were liquid filled, the permeabilitycoefficient ( P) was determined, and then while thetracheae were air filled, the percent clearance for^99mTc-labeleddiethylenetriaminepentaacetic acid (DTPA) was determined. The thicknessof airway surface liquid (ASL) was estimated by three methods.1) The initial concentration of^99mTc-DTPA and the total amount of^99mTc-DTPA (the sum of thatentering the outside medium, that draining from the trachea, and thatwashed out at the end of 40 min) gave the initial volume of ASL andthus its thickness. Mean values were 45.7 µm for the ferret and 41.9 µm for the rabbit. 2) Estimates ofASL thickness at the end of the 40-min period, based on the final^99mTc-DTPA concentration and theamount in the washout, were 42.9 µm for ferret and 45.4 µm forrabbit. 3) The ratio of Pto percent clearance gave mean ASL thickness values of 49.2 µm forthe ferret and 40.3 µm for the rabbit. Thus three separate methodsfor determining ASL thickness give very similar results, with means inthe range 40-49 µm. Administration of methacholine or atropineto ferret tracheae did not significantly change ASL thickness.

     

Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat

We used the microdialysis technique to measurethe interstitial concentration of several putative metabolic stimulantsof the exercise pressor reflex during 3- and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart rate and mean arterial pressure during contraction were 20 ± 5 beats/min and 21 ± 8 mmHg and 27 ± 9 beats/min and 37 ± 12 mmHg for the 3- and 5-Hz stimulation protocols, respectively. All variables returned tobaseline after 10 min of recovery. Interstitial lactate rose (P < 0.05) by 0.41 ± 0.15 and0.56 ± 0.16 mM for the 3- and 5-Hz stimulation protocols,respectively, and were not statistically different from one another.Interstitial lactate levels remained above(P < 0.05) baseline during recoveryin the 5-Hz group. Dialysate phosphate concentrations (corrected forshifts in probe recovery) rose with stimulation(P < 0.05) by 0.19 ± 0.08 and0.11 ± 0.03 mM for the 3- and 5-Hz protocols. There were nodifferences between groups. The resting dialysateK⁺ concentrations for the 3- and5-Hz conditions were 4.0 ± 0.1 and 3.9 ± 0.1 meq/l,respectively. During stimulation the dialysate K⁺ concentrations rose steadilyfor both conditions, and the increase from rest to stimulation(P < 0.05) was 0.57 ± 0.19 and0.81 ± 0.06 meq/l for the 3- and 5-Hz conditions, respectively,with no differences between groups. Resting dialysate pH was6.915 ± 0.055 and 6.981 ± 0.032 and rose to 7.013 (P < 0.05) and 7.053 (P < 0.05) for the 3- and 5-Hzconditions, respectively, and then became acidotic (6.905, P < 0.05) during recovery (5 Hzonly). This study represents the first time simultaneous measurements of multiple skeletal muscle interstitial metabolites and pressor responses to twitch contractions have been made in the cat. These datasuggest that interstitial K⁺ andphosphate, but not lactate and H⁺,may contribute to the stimulation of thin fiber muscle afferents duringcontraction.