Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction

Charan, Nirmal B., and Paula Carvalho. Angiogenesis inbronchial circulatory system after unilateral pulmonary artery obstruction. J. Appl. Physiol. 82(1):284-291, 1997.We studied the effects of left pulmonary artery(LPA) ligation on the bronchial circulatory system (BCS) by using asheep model. LPA was ligated in the newborn lambs soon after birth(n = 8), and when the sheep were ~3yr of age anatomic studies revealed marked angiogenesis in BCS.Bronchial blood flow and cardiac output were studied by placing flowprobes around the bronchial and pulmonary arteries in four adult sheep.After LPA ligation, bronchial blood flow increased from 35 ± 6 to134 ± 42 ml/min in ~3 wk (P < 0.05). We also studied gas-exchange functions of BCS ~3 yr after the ligation of LPA in newborn lambs (n = 4) and used a control group (n = 12)in which LPA was ligated acutely. In the left lung,O₂ uptake after acute ligation was16 ± 3 ml/min and was similar to the chronic model, whereasCO₂ output in the control group was 27 ± 3 ml/min compared with 79 ± 12 ml/min in the chronic preparation (P < 0.05).We conclude that LPA ligation causes marked angiogenesis in BCS that iscapable of performing some gas-exchange functions.

     

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

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

     

Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar hypoxia

Albert, T. S. E., V. L. Tucker, and E. M. Renkin.Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar hypoxia. J. Appl.Physiol. 82(1): 102-110, 1997.Arterial oxygentensions (Pa_O2), atrial natriureticpeptide (ANP) concentrations, and circulating plasma volumes (PV) weremeasured in anesthetized rats ventilated with room air or 15, 10, or8% O₂(n = 5-7). After 10 min ofventilation, Pa_O2 values were 80 ± 3, 46 ± 1, 32 ± 1, and 35 ± 1 Torrand plasma immunoreactive ANP (irANP) levels were 211 ± 29, 229 ± 28, 911 ± 205, and 4,374 ± 961 pg/ml, respectively. AtPa_O2 40 Torr, irANP responses weremore closely related to inspiredO₂(P = 0.014) than toPa_O2 (P = 0.168). PV was 36.3 ± 0.5 µl/g in controls but 8.5 and9.9% lower (P  0.05) for10 and 8% O₂, respectively.Proportional increases in hematocrit were observed in animals withreduced PV; however, plasma protein concentrations were not differentfrom control. Between 10 and 50 min of hypoxia, small increases (+40%)in irANP occurred in 15% O₂;however, there was no further change in PV, hematocrit, plasma protein,or irANP levels in the lower O₂groups. Urine output tended to fall during hypoxia but was notsignificantly different among groups. These findings are compatiblewith a role for ANP in mediating PV contraction during acute alveolarhypoxia.

     

Ovine fetal adaptations to chronically reduced urine flow: preservation of amniotic fluid volume

Mann, Stephanie E., Mark J. M. Nijland, and Michael G. Ross.Ovine fetal adaptations to chronically reduced urine flow: preservation of amniotic fluid volume. J. Appl.Physiol. 81(6): 2588-2594, 1996.Adequateamniotic fluid (AF) volume is maintained by a balance of fetal fluidproduction (lung liquid and urine) and resorption (swallowing andintramembranous flow). Because fetal urine is the principle source ofAF, alterations in urine flow and composition directly impact AFdynamics. Intra-amniotic 1-desamino-8-D-argininevasopressin (DDAVP) is rapidly absorbed into fetal plasma and induces amarked fetal urinary antidiuresis. To examine the effect ofintra-amniotic- DDAVP-induced fetal urinary responses on AF volume andcomposition, six chronically prepared ewes with singleton fetuses(gestation 128 ± 2 days) were studied for 72 h after a singleintra-amniotic DDAVP (50-µg) injection. After DDAVP, fetal urineosmolality significantly increased at 2 h (157 ± 13 to 253 ± 21 mosmol/kg) and remained elevated at 72 h (400 ± 13 mosmol/kg). Urinary sodium (33.0 ± 4.5 to 117.2 ± 9.7 meq/l)and chloride (26.0 ± 2.8 to 92.4 ± 8.1 meq/l) concentrations similarly increased. AF osmolality increased (285 ± 3 to 299 ± 4 mosmol/kgH₂O), although there was no change in fetalplasma osmolality (294 ± 2 mosmol/kg). Despite a 50% reductionin fetal urine flow (0.12 ± 0.03 to 0.05 ± 0.02 ml ^· kg^{1 ·} min¹at 2 h and 0.06 ± 0.01 ml ^· kg^{1 ·} min¹after 72 h), AF volume did not change (693 ± 226 to 679 ± 214 ml). There were no changes in fetal arterial blood pressures, pH,PCO₂, orPO₂ after DDAVP. We conclude the following. 1)Intra-amniotic DDAVP injection induces a prolonged decrease in fetalurine flow and increases in urine and AF osmolalities. 2) Despite decreased urine flow, AFvolume does not change. We speculate that, in response to DDAVP-inducedfetal oliguria, reversed intramembranous flow (from isotonic fetalplasma to hypertonic AF) preserves AF volume.

     

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

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

     

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

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

     

Effects of gender on resting leg blood flow: implications for measurement of regional substrate oxidation

Jensen, Michael D., Tu T. Nguyen, A. HernándezMijares, C. Michael Johnson, and Michael J. Murray. Effects ofgender on resting leg blood flow: implications for measurement ofregional substrate oxidation. J. Appl.Physiol. 84(1): 141-145, 1998.These studies weredesigned to examine whether the respiratory quotient (RQ) of leg tissue(primarily skeletal muscle) would increase to a greater degree in womenthan in men during meal ingestion. We found that mean leg and systemicRQ values were similar in men under both basal and fed conditions,whereas the agreement was poor in women. In women, leg RQ values tendedto be greater than the systemic RQ, whereas splanchnic RQ values tendedto be lower than the systemic RQ. The possibility that measurementimprecision accounted for the different findings in women could not beexcluded because the arteriovenous bloodO₂ differences were almost twice as great in men as in women (53.7 ± 5.4 vs. 28.6 ± 2.9 ml ofO₂/l, respectively;P < 0.01), as were venoarterialblood CO₂ differences. The smallerarteriovenous differences in women appeared to limit our ability toaccurately measure their leg RQ values.O₂ uptake relative to leg fat-freemass (FFM) was not different between men and women, whereas leg bloodflow relative to leg FFM was greater in women than in men (55 ± 3vs. 39 ± 2 ml · kgFFM¹ · min¹,respectively; P < 0.001). Thesefindings were confirmed by examining data from other studies conductedin our laboratory to create a larger data set. We conclude that restingleg blood flow in women is greater (relative to FFM) than in men,making it more difficult to accurately measure leg RQ in women.

     

Age alters the cardiovascular response to direct passive heating

Duringdirect passive heating in young men, a dramatic increase in skin bloodflow is achieved by a rise in cardiac output (_c) andredistribution of flow from the splanchnic and renal vascular beds. Toexamine the effect of age on these responses, seven young (Y; 23 ± 1 yr) and seven older (O; 70 ± 3 yr) men were passively heated withwater-perfused suits to their individual limit of thermal tolerance.Measurements included heart rate (HR), _c (byacetylene rebreathing), central venous pressure (via peripherally inserted central catheter), blood pressures (by brachial auscultation), skin blood flow (from increases in forearm blood flow by venous occlusion plethysmography), splanchnic blood flow (by indocyanine green clearance), renal blood flow (byp-aminohippurateclearance), and esophageal and mean skin temperatures._c wassignificantly lower in the older than in the young men (11.1 ± 0.7 and 7.4 ± 0.2 l/min in Y and O, respectively, at the limit ofthermal tolerance; P < 0.05),despite similar increases in esophageal and mean skin temperatures andtime to reach the limit of thermal tolerance. A lower stroke volume (99 ± 7 and 68 ± 4 ml/beat in Y and O, respectively, P < 0.05), most likely due to anattenuated increase in inotropic function during heating, was theprimary factor for the lower _c observed inthe older men. Increases in HR were similar in the young and older men;however, when expressed as a percentage of maximal HR, the older menrelied on a greater proportion of their chronotropic reserve to obtainthe same HR response (62 ± 3 and 75 ± 4% maximal HR in Y andO, respectively, P < 0.05). Furthermore, the older men redistributed less blood flow from thecombined splanchnic and renal circulations at the limit of thermaltolerance (960 ± 80 and 720 ± 100 ml/min in Y and O,respectively, P < 0.05). As a resultof these combined attenuated responses, the older men had asignificantly lower increase in total blood flow directed to the skin.

     

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.

     

Transcapillary escape rate of albumin in humans during exercise-induced hypervolemia

Haskell, Andrew, Ethan R. Nadel, Nina S. Stachenfeld, KeiNagashima, and Gary W. Mack. Transcapillary escape rate of albuminin humans during exercise-induced hypervolemia. J. Appl. Physiol. 83(2): 407-413, 1997.To test thehypotheses that plasma volume (PV) expansion 24 h after intenseexercise is associated with reduced transcapillary escape rate ofalbumin (TER_alb) and that localchanges in transcapillary forces in the previously active tissues favorretention of protein in the vascular space, we measured PV,TER_alb, plasma colloid osmoticpressure (COP_p), interstitialfluid hydrostatic pressure (Pi), and colloid osmotic pressure in legmuscle and skin and capillary filtration coefficient (CFC) in the armand leg in seven men and women before and 24 h after intense uprightcycle ergometer exercise. Exercise expanded PV by 6.4% at 24 h (43.9 ± 0.8 to 46.8 ± 1.2 ml/kg, P < 0.05) and decreased total protein concentration (6.5 ± 0.1 to6.3 ± 0.1 g/dl, P < 0.05) andCOP_p (26.1 ± 0.8 to 24.3 ± 0.9 mmHg, P < 0.05), although plasmaalbumin concentration was unchanged. TER_alb tended to decline (8.4 ± 0.5 to 6.5 ± 0.7%/h, P = 0.11) and was correlated with the increase in PV(r = 0.69,P < 0.05). CFC increased in the leg(3.2 ± 0.2 to 4.3 ± 0.5 µl · 100 g¹ · min¹ · mmHg¹,P < 0.05), and Pi showed a trend toincrease in the leg muscle (2.8 ± 0.7 to 3.8 ± 0.3 mmHg, P = 0.08). These datademonstrate that TER_alb isassociated with PV regulation and that local transcapillary forcesin the leg muscle may favor retention of albumin in the vascular spaceafter exercise.

     

Endothelin blockade augments pulmonary vasodilation in the ovine fetus

Ivy, D. Dunbar, John P. Kinsella, and Steven H. Abman.Endothelin blockade augments pulmonary vasodilation in the ovine fetus. J. Appl. Physiol. 81(6):2481-2487, 1996.The physiological role of endothelin-1 (ET-1) inregulation of vascular tone in the perinatal lung is controversial.Recent studies suggest that ET-1 contributes to high basal pulmonaryvascular resistance in the normal fetus, but its role in the modulationof pulmonary vascular tone remains uncertain. We hypothesized that highET-1 activity opposes the vasodilator response to some physiological stimuli such as increased pressure. To test the hypothesis that ET-1modulates fetal pulmonary vascular responses to acute and prolongedphysiological stimuli, we performed a series of experiments in thelate-gestation ovine fetus. We studied the hemodynamic effects of twoET-1 antagonists, BQ-123 (a selectiveET_A-receptor antagonist) andphosphoramidon (a nonselective ET-1-converting enzyme inhibitor) duringmechanical increases in pressure due to partial ductus arteriosuscompression in chronically prepared late-gestation fetal lambs. Incontrol studies, partial ductus arteriosus compression decreased theratio of pulmonary arterial pressure to pulmonary artery flow in theleft lung 34 ± 6% from baseline. Intrapulmonary infusions ofBQ-123 (0.5 µg/min for 10 min; 0.025 µg/min for 2 h) orphosphoramidon (1.0 mg/min for 10 min) augmented the peak vasodilatorresponse during ductus arteriosus compression (52 ± 3 and 49 ± 6% from baseline, respectively, P < 0.05 vs. control). In addition, unlike the transient vasodilator response to ductus arteriosus compression in control studies, ET-1blockade with BQ-123 or phosphoramidon prolonged the increase in flowcaused by ductus arteriosus compression. In summary,ET_A-receptor blockade andET-1-converting enzyme inhibition augment and prolong fetal pulmonaryvasodilation during partial compression of the ductus arteriosus. Weconclude that ET-1 activity modulates acute and prolonged responses ofthe fetal pulmonary circulation to changes in vascular pressure. Wespeculate that ET-1 contributes to regulation and maintenance of highpulmonary vascular resistance in the normal ovine fetal lung.

     

Optical measurement of isolated canine lung filtration coefficients at normal hematocrits

Klaesner, Joseph W., N. Adrienne Pou, Richard E. Parker,Charlene Finney, and Robert J. Roselli. Optical measurement ofisolated canine lung filtration coefficients at normal hematocrits. J. Appl. Physiol. 83(6):1976-1985, 1997.In this study, lung filtration coefficient(K_fc) valueswere measured in eight isolated canine lung preparations at normalhematocrit values using three methods: gravimetric, blood-correctedgravimetric, and optical. The lungs were kept in zone 3 conditions andsubjected to an average venous pressure increase of 10.24 ± 0.27 (SE) cmH₂O. The resulting K_fc(ml · min¹ · cmH₂O¹ · 100 g dry lung wt¹) measuredwith the gravimetric technique was 0.420 ± 0.017, which wasstatistically different from theK_fc measured bythe blood-corrected gravimetric method (0.273 ± 0.018) or theproduct of the reflection coefficient(_f) andK_fc measuredoptically (0.272 ± 0.018). The optical method involved the use of aCellco filter cartridge to separate red blood cells from plasma, whichallowed measurement of the concentration of the tracer in plasma atnormal hematocrits (34 ± 1.5). The permeability-surface areaproduct was measured using radioactive multiple indicator-dilutionmethods before, during, and after venous pressure elevations. Resultsshowed that the surface area of the lung did not change significantlyduring the measurement ofK_fc. Thesestudies suggest that_fK_fccan be measured optically at normal hematocrits, that this measurement is not influenced by blood volume changes that occur during the measurement, and that the optical_fK_fcagrees with theK_fc obtained viathe blood-corrected gravimetric method.

     

Acute alveolar hypoxia increases blood-to-tissue albumin transport: role of atrial natriuretic peptide

Albert, T. S. E., V. L. Tucker, and E. M. Renkin. Acutealveolar hypoxia increases blood-to-tissue albumin transport: role ofatrial natriuretic peptide. J. Appl.Physiol. 82(1): 111-117, 1997.Plasmaimmunoreactive atrial natriuretic peptide (irANP) and blood-to-tissueclearance of ¹³¹I-labeled ratserum albumin (C_RSA) wereexamined in anesthetized rats during hypoxic ventilation(n = 5-7/group). Hypoxia (10 min) increased irANP from 211 ± 29 (room air) to 229 ± 28 (15%O₂, not significant), 911 ± 205 (10% O₂), and 4,374 ± 961 pg/ml (8% O₂),respectively. Graded increases inC_RSA were significant at 8%O₂ in fat (3.6-fold), ileum(2.2-fold), abdominal muscles (2.0-fold), kidney (1.8-fold), andjejunum (1.4-fold). C_RSA wasdecreased in back skin and testes; heart, brain, and lungs wereunaffected. The increases in C_RSAwere related to irANP and not to arterial PO₂. Circulating plasma volume wasnegatively correlated with whole bodyC_RSA. Graded increases inextravascular water content (EVW) were found in the kidney, left heart,and cerebrum and were positively related toC_RSA in the kidney. EVW decreased in gastrointestinal tissues; the magnitude was inversely related toC_RSA. We conclude that ANP-inducedprotein extravasation contributes to plasma volume contraction duringacute hypoxia.

     

Systemic and myocardial hemodynamics during periodic obstructive apneas in sedated pigs

The effects of periodic obstructive apneas onsystemic and myocardial hemodynamics were studied in ninepreinstrumented sedated pigs under four conditions: breathing room air(RA), breathing 100% O₂,breathing RA after critical coronary stenosis (CS) of the left anteriordescending coronary artery, and breathing RA after autonomic blockadewith hexamethonium (Hex). Apneas with RA increased mean arterialpressure (MAP; from baseline 103.0 ± 3.5 to late apnea 123.6 ± 7.0 Torr, P < 0.001) and coronary blood flow (CBF; late apnea 193.9 ± 22.9% of baseline,P < 0.001) but decreased cardiacoutput (CO; from baseline 2.97 ± 0.15 to late apnea 2.39 ± 0.19 l/min, P < 0.001). Apneas withO₂ increased MAP (from baseline105.1 ± 4.6 to late apnea 110.7 ± 4.8 Torr, P < 0.001). Apneas with CS producedsimilar increases in MAP as apneas with RA but greater decreases in CO(from baseline 3.03 ± 0.19 to late apnea 2.1 ± 0.15 l/min,P < 0.001). In LAD-perfused myocardium, there was decreased segmental shortening (baseline 11.0 ± 1.5 to late apnea 7.6 ± 2.0%,P < 0.01) and regionalintramyocardial pH (baseline 7.05 ± 0.03 to late apnea 6.72 ± 0.11, P < 0.001) during apneas withCS but under no other conditions. Apneas with Hex increased to the sameextent as apneas with RA. Myocardial O₂ demand remained unchangedduring apnea relative to baseline. We conclude that obstructiveapnea-induced changes in left ventricular afterload and CO aresecondary to autonomic-mediated responses to hypoxemia. Increased CBFduring apneas is related to regional metabolic effects of hypoxia andnot to autonomic factors. In the presence of limited coronary flowreserve, decreased O₂ supply during apneas can lead to myocardial ischemia, which in turnadversely affects left ventricular function.

     

Abdominal muscle fatigue after maximal ventilation in humans

Kyroussis, Dimitris, Gary H. Mills, Michael I. Polkey,Carl-Hugo Hamnegard, Nicholaos Koulouris, Malcolm Green, and John Moxham. Abdominal muscle fatigue after maximal ventilation inhumans. J. Appl. Physiol. 81(4):1477-1483, 1996.Abdominal muscles are the principal muscles ofactive expiration. To investigate the possibility of abdominal musclelow-frequency fatigue after maximal ventilation in humans, westimulated the nerve roots supplying the abdominal muscles. We used amagnetic stimulator (Magstim 200) powering a 90-mm circular coil andstudied six normal subjects. To assess the optimum level of stimulationand posture, we stimulated at each intervertebral level betweenT₇ andL₁ in the prone, supine, andseated positions. At T₁₀, we usedincreasing power outputs to assess the pressure-power relationship.Care was taken to avoid muscle potentiation. Twitch gastric pressure(Pga) was recorded with a balloon-tipped catheter. Mean (±SD)baseline twitch Pga measured with the subjects in the prone position atT₁₀ was 23.5 ± 5.4 cmH₂O. Within-occasion mean twitchPga coefficient of variation was 4.6 ± 1.1%. Twitch Pga wasmeasured with the subjects in the prone position with stimulation overT₁₀ before and after 2 min ofmaximal isocapnic ventilation (MIV). Twenty minutes after MIV, meantwitch Pga fell by 17 ± 9.1%(P = 0.03) and remained low 90 minafter MIV. We conclude that after maximal ventilation in humans thereis a reduction of twitch Pga and, therefore, of low-frequency fatiguein abdominal muscles.

     

Cyclooxygenase inhibition potentiates the renal vascular response to endothelin-1 in humans

Vascular endothelin-receptor stimulation resultsin vasoconstriction and concomitant production of the vasodilatorsprostaglandin I₂ and nitric oxide.The vascular effects of cyclooxygenase (COx) blockade (diclofenacintravenously) and the subsequent vasoconstrictor response toendothelin-1 (ET-1) infusion 30 min after diclofenac were studied inhealthy men. With COx blockade, cardiac output (7%) and splanchnic(14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flowreturned to basal value within 30 min. Mean arterial blood pressureincreased (4%, P < 0.001). Splanchnic glucose output fell (22%,P < 0.01). Subsequent ET-1 infusioncaused, compared with previous ET-1 infusion without COx blockade (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl.Physiol. 77: 121-126, 1994; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Biochem. Biophys. Res.Commun. 180: 1298-1303, 1991; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Clin.Physiol. (Colch.) 13: 653-662, 1993),the same increase in mean arterial blood pressure (4%), decreases incardiac output (13%) and splanchnic blood flow (38%), but nosignificant change in splanchnic glucose output. Renal blood flowreduction was potentiated (33 ± 3 vs. 23 ± 2%,P < 0.02), with a total reductioncorresponding to 43 ± 3%(P < 0.01 vs. 23 ± 3%). Weconclude that COx inhibition induces renal and splanchnicvasoconstriction. The selectively increased renal vascularresponsiveness to ET-1 emphasizes the importance of endogenousarachidonic acid metabolites (i.e., prostaglandin I₂) to counteract ET-1-mediatedrenal vasoconstriction.

     

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.     

Skeletal muscle ECF pH error signal for exercise ventilatory control

Evans, Allison B., Larry W. Tsai, David A. Oelberg, HomayounKazemi, and David M. Systrom. Skeletal muscle ECF pH error signalfor exercise ventilatory control. J. Appl.Physiol. 84(1): 90-96, 1998.An autonomic reflexlinking exercising skeletal muscle metabolism to central ventilatorycontrol is thought to be mediated by neural afferents having freeendings that terminate in the interstitial fluid of muscle. Todetermine whether changes in muscle extracellular fluid pH(pH_e) can provide an errorsignal for exercise ventilatory control,pH_e was measured duringelectrically induced contraction by³¹P-magnetic resonancespectroscopy and the chemical shift of a phosphorylated, pH-sensitivemarker that distributes to the extracellular fluid (phenylphosphonicacid). Seven lightly anesthetized rats underwentunilateral continuous 5-Hz sciatic nerve stimulation in an 8.45-Tnuclear magnetic resonance magnet, which resulted in a mixed lacticacidosis and respiratory alkalosis, with no net change in arterial pH.Skeletal muscle intracellular pH fell from 7.30 ± 0.03 units atrest to 6.72 ± 0.05 units at 2.4 min of stimulation and then roseto 7.05 ± 0.01 units (P < 0.05), despite ongoing stimulation and muscle contraction.Despite arterial hypocapnia, pH_eshowed an immediate drop from its resting baseline of 7.40 ± 0.01 to 7.16 ± 0.04 units (P < 0.05)and remained acidic throughout the stimulation protocol. During the on-and off-transients for 5-Hz stimulation, changes in the pH gradientbetween intracellular and extracellular compartments suggestedtime-dependent recruitment of sarcolemmal ion-transport mechanisms.pH_e of exercising skeletal musclemeets temporal and qualitative criteria necessary for a ventilatorymetaboreflex mediator in a setting where arterial pH doesnot.

     

Posthemorrhagic antipyresis: what stage of fever genesis is affected?

Romanovsky, Andrej A., and Yelena K. Karman.Posthemorrhagic antipyresis: what stage of fever genesis isaffected? J. Appl. Physiol. 83(2):359-365, 1997.It has been shown that hemorrhage leads to adecreased thermal responsiveness to lipopolysaccharide (LPS). The aimof this study was to clarify what stage of fever genesis[production of endogenous pyrogens such as interleukin-1 (IL-1),increase of the prostaglandin E₂(PGE₂) concentration in braintissue, activation of cold-defense effectors] is deficient inposthemorrhagic antipyresis. In adult rabbits, we evaluated the effectof acute hemorrhage (15 ml/kg) on the rectal temperature (T_re) responses to LPS fromSalmonella typhi (200 ng/kg iv),ethanol-purified preparation of homologous IL-1 (1 ml from 3.5 × 10⁷ cells, 1.5 ml/kg iv), andPGE₂ (1 µg,intracisternal injection). The effect of hemorrhage onT_re was also studied in afebrilerabbits, both at thermoneutrality (23°C) and during ramp cooling(to 7°C). The hemorrhage strongly attenuated the biphasicLPS-induced fever (a T_re rise of0.4 ± 0.1 instead of 1.2 ± 0.2°C at the time of the secondpeak), the monophasic T_re responseto IL-1 (by ~0.5°C for over 1-5 h postinjection), and thePGE₂-induced hyperthermia (0.4 ± 0.1 vs. 0.9 ± 0.1°C, maxima). In afebrileanimals, the hemorrhage neither affectedT_re at thermoneutrality norchanged the T_re response to coldexposure. The data suggest that neither insufficiency of cold-defenseeffectors nor lack of endogenous mediators of fever (IL-1,PGE₂) can be the only or eventhe major cause of posthemorrhagic antipyresis. Wespeculate that fever genesis is altered at a stage occurring after theintrabrain PGE₂ level is increasedbut before thermoeffectors are activated.

     

High-energy phosphates and tension production in rabbit tibialis anterior/extensor digitorum longus muscles

Ryschon, T. W., J. C. Jarvis, S. Salmons, and R. S. Balaban.High-energy phosphates and tension production in rabbit tibialisanterior/extensor digitorum longus muscles. J. Appl. Physiol. 82(3): 1024-1029, 1997.The effects ofrepetitive muscle contraction on energy state and tension productionwere studied in rabbit tibialis anterior/extensor digitorum longusmuscles that had been subjected to 90 days of continuous indirectelectrical stimulation at 10 Hz. Anesthetized chronically stimulatedand control rabbits were challenged with 15 min of stimulation at 4 and15 tetani/min.P_i-to-phosphocreatine (PCr) ratio(P_i/PCr) was measured in vivo before, during, andafter acute stimulation by³¹P-magnetic resonancespectroscopy, and tension was recorded at the same time. AlthoughP_i/PCr was low at rest, it wassignificantly higher in chronically stimulated muscle than in controlmuscle (0.20 ± 0.02 vs. 0.05 ± 0.01, P < 0.05). Stimulation of control muscle for 15 min at both 4 and 15 tetani/min induced a significant rise in P_i/PCr, whereas the sameconditions in chronically stimulated muscle did not produce anysignificant departure from initial levels. The tension produced bycontrol muscle fell to 93 ± 3% of its initial value duringstimulation at 4 tetani/min and to 61 ± 7% at 15 tetani/min,respectively. In chronically stimulated muscle, on the other hand,tension was potentiated above its initial level at both stimulationrates (135 ± 15 and 138 ± 11%, respectively) and remainedsignificantly elevated throughout each trial. The ability ofchronically stimulated muscle to sustain high levels of activity withminimal perturbations in P_i/PCr ordecrement in tension is attributable to cellular adaptations thatinclude a well-documented increase in oxidative capacity.