Age and gender dependency of baroreflex sensitivity in healthy subjects

Laitinen, Tomi, Juha Hartikainen, Esko Vanninen, LeoNiskanen, Ghislaine Geelen, and Esko Länsimies. Age andgender dependency of baroreflex sensitivity in healthy subjects.J. Appl. Physiol. 84(2): 576-583, 1998.We evaluated the correlates of baroreflex sensitivity (BRS) inhealthy subjects. The study consisted of 117 healthy, normal-weight,nonsmoking male and female subjects aged 23-77 yr. Baroreflexcontrol of heart rate was measured by using the phenylephrinebolus-injection technique. Frequency- and time-domain analysis of heartrate variability and an exercise test were performed. Plasmanorepinephrine, epinephrine, insulin, and arginine vasopressinconcentrations and plasma renin activity were measured. In theunivariate analysis, BRS correlated with age(r = 0.65,P < 0.001), diastolic blood pressure(r = 0.47, P < 0.001), exercise capacity(r = 0.60, P < 0.001), and the high-frequency component of heart rate variability (r = 0.64, P < 0.001). There was also asignificant correlation between BRS and plasma norepinephrine concentration (r = 0.22,P < 0.05) and plasma renin activity (r = 0.32, P < 0.001). According to themultivariate analysis, age and gender were the most importantphysiological correlates of BRS. They accounted for 52% ofinterindividual BRS variation. In addition, diastolic blood pressureand high-frequency component of heart rate variability were significantindependent correlates of BRS. BRS was significantly higher in men thanin women (15.0 ± 1.2 vs. 10.2 ± 1.1 ms/mmHg, respectively;P < 0.01). Twenty-four percent ofwomen >40 yr old and 18% of men >60 yr old had markedly depressedBRS (<3 ms/mmHg). We conclude that physiological factors, particularly age and gender, have significant impact on BRS in healthysubjects. In addition, we demonstrate that BRS values that have beenproposed to be useful in identifying postinfarction patients at highrisk of sudden death are frequently found in healthy subjects.

     

Both physical fitness and acute exercise regulate nitric oxide formation in healthy humans

Jungersten, Lennart, Anneli Ambring, Björn Wall, andÅke Wennmalm. Both physical fitness and acute exerciseregulate nitric oxide formation in healthy humans. J. Appl. Physiol. 82(3): 760-764, 1997.We analyzednitrate, a major stable end product of nitric oxide (NO) metabolism invivo in plasma and urine from groups of healthy subjects with differentworking capacities. Resting plasma nitrate was higher in athleticsubjects than in nonathletic controls [45 ± 2 vs. 34 ± 2 (SE) µM; P < 0.01]. In other subjects, both the resting plasma nitrate level(r = 0.53; P < 0.01) and the urinary excretionof nitrate at rest (r = 0.46; P < 0.01) correlated to thesubjects' peak work rates, as determined by bicycle ergometry. Twohours of physical exercise elevated plasma nitrate by 18 ± 4 (P < 0.01) and 16 ± 6%(P < 0.01), respectively, in athletes and nonathletes, compared with resting nitrate before exercise. We conclude that physical fitness and formation of NO at restare positively linked to each other. Furthermore, a single session ofexercise elicits an acute elevation of NO formation. The observedpositive relation between physical exercise and NO formation may helpto explain the beneficial effects of physical exercise oncardiovascular health.

     

Sympathetic discharge and vascular resistance after bed rest

Shoemaker, J. Kevin, Cynthia S. Hogeman, Urs A. Leuenberger,Michael D. Herr, Kristen Gray, David H. Silber, and Lawrence I. Sinoway. Sympathetic discharge and vascular resistance after bedrest. J. Appl. Physiol. 84(2):612-617, 1998.The effect of 6° head-down-tilt bedrest (HDBR) for 14 days on supine sympathetic discharge andcardiovascular hemodynamics at rest was assessed. Mean arterialpressure, heart rate (n = 25), musclesympathetic nerve activity (MSNA; n = 16) burst frequency, and forearm blood flow(n = 14) were measured, and forearmvascular resistance (FVR) was calculated. Stroke distance,our index of stroke volume, was derived from measurements of aorticmean blood velocity (Doppler) and R-R interval(n = 7). With these data, an index oftotal peripheral resistance was determined. Heart rate at rest wasgreater in the post (71 ± 2 beats/min)- compared with the pre-HDBRtest (66 ± 2 beats/min; P < 0.003), but mean arterial pressure was unchanged. Aortic strokedistance during post-HDBR (15.5 ± 1.1 cm/beat) was reduced frompre-HDBR levels (20.0 ± 1.5 cm/beat)(P < 0.03). Also, MSNA burstfrequency was reduced in the post (16.7 ± 2.8 beats/min)- comparedwith the pre (25.2 ± 2.6 beats/min)-HDBR condition(P < 0.01). Bed rest did not alterforearm blood flow, FVR, or total peripheral resistance. Thusreductions in MSNA with HDBR were not associated with a decrease inFVR.

     

Left ventricular mass, geometry, and filling in endurance athletes: association with exercise blood pressure

Karjalainen, Jouko, Matti Mäntysaari, MattiViitasalo, and Urho Kujala. Left ventricular mass, geometry,and filling in endurance athletes: association with exercise bloodpressure. J. Appl. Physiol. 82(2):531-537, 1997.We studied whether left ventricular (LV) mass andconcentricity [relative myocardial volume (RMV)] areassociated with exercise blood pressure (BP) in athletes. LV structureand filling were evaluated by Doppler echocardiography and BP inmaximal bicycle ergometry and isometric handgrip tests on 32 maleendurance athletes and 15 age-matched controls. Indexed LV mass was 145 ± 14 (SD) g/m in athletes and 93 ± 20 g/m incontrols. Mass was not associated with BP at rest or inlow-grade exercise, but with heavier exercise loads this associationstrengthened in athletes, being maximal at peak exercise(r = 0.65 for mass and 0.58 forindexed mass; P < 0.001). Multivariate analysis indicated that BP at peakexercise accounted for 34% and the amount of training for anadditional 11% of the variance in indexed LV mass. RMV was 21% largerin athletes. Only the increase in systolic BP during handgrip explainedsignificantly (19%) the variance in RMV. LV filling velocities werenot associated with mass, RMV, or BP. We conclude that in enduranceathletes LV mass is associated with BP in heavy dynamic exercise and LVconcentricity with BP response in static exercise.

     

Atrial distension in humans during microgravity induced by parabolic flights

Videbaek, Regitze, and Peter Norsk. Atrialdistension in humans during microgravity induced by parabolic flights.J. Appl. Physiol. 83(6):1862-1866, 1997.The hypothesis was tested that human cardiacfilling pressures increase and the left atrium is distended during 20-speriods of microgravity (µG) created by parabolic flights, comparedwith values of the 1-G supine position. Left atrial diameter(n = 8, echocardiography) increasedsignificantly during µG from 26.8 ± 1.2 to 30.4 ± 0.7 mm(P < 0.05). Simultaneously, centralvenous pressure (CVP; n = 6, transducer-tipped catheter) decreased from 5.8 ± 1.5 to 4.5 ± 1.1 mmHg (P < 0.05), and esophageal pressure (EP; n = 6) decreased from1.5 ± 1.6 to 4.1 ± 1.7 mmHg (P < 0.05). Thus transmural CVP(TCVP = CVP  EP; n = 4)increased during µG from 6.1 ± 3.2 to 10.4 ± 2.7 mmHg(P < 0.05). It is concluded thatshort periods of µG during parabolic flights induce an increase inTCVP and left atrial diameter in humans, compared with the resultsobtained in the 1-G horizontal supine position, despite a decrease inCVP.

     

Myosin molecular motor dysfunction in dystrophic mouse diaphragm

Cross-bridge properties and myosin heavy chain (MHC) compositionwere investigated in isolated diaphragm from 6-mo-old control (n = 12) andmdx(n = 12) mice. Compared with control,peak tetanic tension fell by 50% inmdx mice(P < 0.001). The total number ofcross bridges per square millimeter(×10⁹), the elementaryforce per cross bridge, and the peak mechanical efficiency were lowerin mdx than in control mice (eachP < 0.001). The duration of thecycle and the rate constant for cross-bridge detachment weresignificantly lower in mdx than incontrol mice. In the overall population, there was a linearrelationship between peak tetanic tension and either total number ofcross bridges per square millimeter or elementary force per crossbridge (r = 0.996 andr = 0.667, respectively, eachP < 0.001). Themdx mice presented a higher proportionof type IIA MHC (P < 0.001) thancontrol mice and a reduction in type IIX MHC(P < 0.001) and slowmyosin isoforms (P < 0.01) comparedwith control mice. We concluded that, inmdx mice, impaired diaphragm strengthwas associated with qualitative and quantitative changes in myosin molecular motors. It is proposed that reduced force generated per crossbridge contributed to diaphragm weakness inmdx mice.

     

Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz,R. L. Smith, J. L. Robotham, and C. P. O'Donnell. Systemic andpulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5):1671-1680, 1997.We examined the hemodynamic responses to normalbreathing and induced upper airway obstructions during sleep in acanine model of obstructive sleep apnea. During normal breathing,cardiac output decreased (12.9 ± 3.5%,P < 0.025) from wakefulness tonon-rapid-eye-movement sleep (NREM) but did not change from NREM torapid-eye-movement (REM) sleep. There was a decrease(P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures fromwakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg,P < 0.025), but not pulmonary,arterial pressures decreased from NREM to REM sleep. During repetitiveairway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiacoutput (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased(P < 0.05), without a change instroke volume, compared with normal breathing during NREM sleep. Duringsingle obstructive events, left (7.8 ± 3.0%,P < 0.05) and right (7.1 ± 0.7%, P < 0.01)ventricular outputs decreased during the apneic period. However, left(20.7 ± 1.6%, P < 0.01) andright (24.0 ± 4.2%, P < 0.05)ventricular outputs increased in the postapneic period because of anincrease in heart rate. Thus 1) thesystemic, but not the pulmonary, circulation vasodilates during REMsleep with normal breathing; 2)heart rate, rather than stroke volume, is the dominant factormodulating ventricular output in response to apnea; and3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.

     

Effects of renal denervation on cardiovascular and renal responses to ACE inhibition in conscious lambs

Smith, Francine G., Suzanne Chan, and Saskia N. De Wildt.Effects of renal denervation on cardiovascular and renal responsesto ACE inhibition in conscious lambs. J. Appl.Physiol. 83(2): 414-419, 1997.Cardiovascular andrenal effects of either the angiotensin-converting enzyme inhibitorcaptopril or vehicle were measured in chronically instrumented lambs inthe presence (intact; n = 6) andabsence of renal sympathetic nerves (denervated; n = 5) to determine whether there wasan interaction between the renin-angiotensin system and renalsympathetic nerves early in life. Captopril caused a similar decreasein mean arterial pressure (P < 0.001) in intact and denervated lambs, predominantly through a decreasein diastolic pressure. Heart rate was increased from 177 ± 34 to213 ± 22 (SD) beats/min during captopril compared with vehicleinfusion in intact lambs. In denervated lambs, basal heart rates wereelevated to 218 ± 33 beats/min; there was no further increase inheart rate during captopril compared with vehicle infusion. Captoprilinfusion caused a decrease in renal vascular resistance but only in theabsence of renal nerves. These findings provide evidence to suggestthat early in life there is an interaction between renal sympatheticnerves and the renin-angiotensin system in regulating renalhemodynamics and the baroreflex control of the heart.

     

Prostaglandin production contributes to exercise-induced vasodilation in heart failure

Lang, Chim C., Don B. Chomsky, Javed Butler, Shiv Kapoor,and John R. Wilson. Prostaglandin production contributes toexercise-induced vasodilation in heart failure. J. Appl. Physiol. 83(6): 1933-1940, 1997.Endothelial release of prostaglandins may contribute toexercise-induced skeletal muscle arteriolar vasodilation in patientswith heart failure. To test this hypothesis, we examined the effect ofindomethacin on leg circulation and metabolism in eight chronic heartfailure patients, aged 55 ± 4 yr. Central hemodynamics and legblood flow, determined by thermodilution, and leg metabolic parameterswere measured during maximum treadmill exercise before and 2 h afteroral administration of indomethacin (75 mg). Leg release of6-ketoprostaglandin F₁ was alsomeasured. During control exercise, leg blood flow increased from 0.34 ± 0.03 to 1.99 ± 0.19 l/min(P < 0.001), legO₂ consumption from 13.6 ± 1.8 to 164.5 ± 16.2 ml/min (P < 0.001), and leg prostanoid release from 54.1 ± 8.5 to267.4 ± 35.8 pg/min (P < 0.001).Indomethacin suppressed release of prostaglandinF₁(P < 0.001) throughout exercise anddecreased leg blood flow during exercise(P < 0.05). This was associated witha corresponding decrease in leg O₂ consumption (P < 0.05) and a higher level offemoral venous lactate at peak exercise(P < 0.01). These data suggest thatrelease of vasodilatory prostaglandins contributes to skeletal musclearteriolar vasodilation in patients with heart failure.

     

Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic reflex

Ray, Chester A., and Keith M. Hume. Neck afferents andmuscle sympathetic activity in humans: implications for the vestibulosympathetic reflex. J. Appl.Physiol. 84(2): 450-453, 1998.We have shownpreviously that head-down neck flexion (HDNF) in humans elicitsincreases in muscle sympathetic nerve activity (MSNA). The purpose ofthis study was to determine the effect of neck muscle afferents onMSNA. We studied this question by measuring MSNA before and after headrotation that would activate neck muscle afferents but not thevestibular system (i.e., no stimulation of the otolith organs orsemicircular canals). After a 3-min baseline period with the head inthe normal erect position, subjects rotated their head to the side(~90°) and maintained this position for 3 min. Head rotation wasperformed by the subjects in both the prone(n = 5) and sitting(n = 6) positions. Head rotation did not elicit changes in MSNA. Average MSNA, expressed asburst frequency and total activity, was 13 ± 1 and 13 ± 1 bursts/min and 146 ± 34 and 132 ± 27 units/min during baselineand head rotation, respectively. There were no significant changes incalf blood flow (2.6 ± 0.3 to 2.5 ± 0.3 ml · 100 ml¹ · min¹;n = 8) and calf vascular resistance(39 ± 4 to 41 ± 4 units; n = 8). Heart rate (64 ± 3 to 66 ± 3 beats/min;P = 0.058) and mean arterial pressure(90 ± 3 to 93 ± 3; P < 0.05)increased slightly during head rotation. Additional neck flexionstudies were performed with subjects lying on their side(n = 5). MSNA, heart rate, and meanarterial pressure were unchanged during this maneuver, which also doesnot engage the vestibular system. HDNF was tested in 9 of the 13 subjects. MSNA was significantly increased by 79 ± 12% (P < 0.001) during HDNF. Thesefindings indicate that neck afferents activated by horizontal neckrotation or flexion in the absence of significant force development donot elicit changes in MSNA. These findings support the concept thatHDNF increases MSNA by the activation of the vestibular system.

     

Augmentation of exercise-induced muscle sympathetic nerve activity during muscle heating

Ray, Chester A., and Kathryn H. Gracey. Augmentation ofexercise-induced muscle sympathetic nerve activity during muscle heating. J. Appl. Physiol. 82(6):1719-1725, 1997.The muscle metabo- and mechanoreflexes have beenshown to increase muscle sympathetic nerve activity (MSNA) duringexercise. Group III and IV muscle afferents, which are believed tomediate this response, have been shown to be thermosensitive inanimals. The purpose of the present study was to evaluate the effect ofmuscle temperature on MSNA responses during exercise. Eleven subjectsperformed ischemic isometric handgrip at 30% of maximal voluntarycontraction to fatigue, followed by 2 min of postexercise muscleischemia (PEMI), with and without local heating of the forearm. Localheating of the forearm increased forearm muscle temperature from 34.4 ± 0.2 to 38.9 ± 0.3°C(P = 0.001). Diastolic andmean arterial pressures were augmented during exercise in the heat.MSNA responses were greater during ischemic handgrip with local heatingcompared with control (no heating) after the first 30 s. MSNA responsesat fatigue were greater during local heating. MSNA increased by 16 ± 2 and 20 ± 2 bursts per 30 s for control and heating,respectively (P = 0.03). Whenexpressed as a percent change in total activity (total burstamplitude), MSNA increased 531 ± 159 and 941 ± 237% forcontrol and heating, respectively (P = 0.001). However, MSNA was not different during PEMI between trials.This finding suggests that the augmentation of MSNA during exercisewith heat was due to the stimulation of mechanically sensitive muscleafferents. These results suggest that heat sensitizes skeletal muscleafferents during muscle contraction in humans and may play a role inthe regulation of MSNA during exercise.

     

Depressed ventilatory response to hypoxia in hypothermic newborn piglets: role of glutamate

To evaluatewhether changes in extracellular glutamate (Glu) levels in the centralnervous system could explain the depressed hypoxic ventilatory responsein hypothermic neonates, 12 anesthetized, paralyzed, and mechanicallyventilated piglets <7 days old were studied. The Glu levels in thenucleus tractus solitarius obtained by microdialysis, minute phrenicoutput (MPO), O₂ consumption, arterial blood pressure, heart rate, and arterial blood gases weremeasured in room air and during 15 min of isocapnic hypoxia (inspiredO₂ fraction = 0.10) at braintemperatures of 39.0 ± 0.5°C [normothermia (NT)]and 35.0 ± 0.5°C [hypothermia (HT)]. During NT, MPO increased significantly during hypoxia and remained above baseline. However, during HT, there was a marked decrease in MPOduring hypoxia (NT vs. HT, P < 0.03). Glu levels increased significantly in hypoxia during NT;however, this increase was eliminated during HT(P < 0.02). A significant linearcorrelation was observed between the changes in MPO and Glu levelsduring hypoxia (r = 0.61, P < 0.0001). Changes in pH, arterialPO₂, O₂ consumption, arterial bloodpressure, and heart rate during hypoxia were not different between theNT and HT groups. These results suggest that the depressed ventilatoryresponse to hypoxia observed during HT is centrally mediated and inpart related to a decrease in Glu concentration in the nucleus tractussolitarius.

     

Nature and site of action of endogenous nitric oxide in vasculature of isolated pig lungs

Cremona, George, Tim Higenbottam, Motoshi Takao, Edward A. Bower, and Leslie W. Hall. Nature and site of action of endogenousnitric oxide in vasculature of isolated pig lungs. J. Appl. Physiol. 82(1): 23-31, 1997.The site ofaction of endogenous and exogenous nitric oxide (NO) in isolated piglungs was investigated by using arterial, double, and venous occlusion,which allowed precapillary, postcapillary, and venous segments to bepartitioned into arterial, precapillary, postcapillary, and venoussegments. N^G-nitro-L-arginine(L-NNA;10⁵ M) increased resistancein the arterial (35 ± 6.6%, P = 0.003), precapillary (39.3 ± 5.1%,P = 0.001), and venous (18.3 ± 4.8%, P = 0.01) segments,respectively. Sodium nitroprusside(10⁵ M) and NO (80 parts/million) reversed the effects ofL-NNA. Total pulmonary vascularresistance fell with increasing flow, due to a fall in precapillaryresistance and dynamic resistance, and was significantlylower than mean total resistance.L-NNA increased the resistancesbut did not alter the pattern of the pressure-flow relationships. It isconcluded that, in isolated pig lungs, the effect of endogenous NOseems to be dependent on flow in the arterial segment and independentof flow in the precapillary segment, but variation of its release doesnot appear to be fundamental to accommodation to changes in steadyflow.

     

Role of inhibition of nitric oxide production in monocrotaline-induced pulmonary hypertension

Mathew, Rajamma, Elizabeth S. Gloster, T. Sundararajan, Carl I. Thompson, Guillermo A. Zeballos, andMichael H. Gewitz. Role of inhibition of nitric oxide productionin monocrotaline-induced pulmonary hypertension. J. Appl. Physiol. 82(5): 1493-1498, 1997.Monocrotaline (MCT)-induced pulmonary hypertension (PH) isassociated with impaired endothelium-dependent nitric oxide(NO)-mediated relaxation. To examine the role of NO in PH,Sprague-Dawley rats were given a single subcutaneous injection ofnormal saline [control (C)], 80 mg/kg MCT, or the same doseof MCT and a continuous subcutaneous infusion of 2 mg · kg¹ · day¹of molsidomine, a NO prodrug (MCT+MD). Two weeks later, plasma NO₃ levels, pulmonary arterialpressure (Ppa), ratio of right-to-left ventricular weights (RV/LV) toassess right ventricular hypertrophy, and pulmonary histology wereevaluated. The plasma NO₃ level inthe MCT group was reduced to 9.2 ± 1.5 µM(n = 12) vs. C level of 17.7 ± 1.8 µM (n = 8; P < 0.02). In the MCT+MD group,plasma NO₃ level was 12.3 ± 2.0 µM (n = 8). Ppa and RV/LV in theMCT group were increased compared with C [Ppa, 34 ± 3.4 mmHg(n = 6) vs. 19 ± 0.8 mmHg(n = 8) and 0.41 ± 0.01 (n = 9) vs. 0.25 ± 0.008 (n = 8), respectively;P < 0.001]. In the MCT+MDgroup, Ppa and RV/LV were not different when compared with C [19 ± 0.5 mmHg (n = 5) and 0.27 ± 0.01 (n = 9), respectively;P < 0.001 vs. MCT]. Medial wall thickness of lung vessels in the MCT group was increased comparedwith C [31 ± 1.5% (n = 9)vs. 13 ± 0.66% (n = 9);P < 0.001], and MDpartially prevented MCT-induced pulmonary vascular remodeling [22 ± 1.2% (n = 11);P < 0.001 vs. MCT and C].These results indicate that a defect in the availability of bioactive NO may play an important role in the pathogenesis of MCT-induced PH.

     

Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle

Edwards, N., I. Wilcox, O. J. Polo, and C. E. Sullivan.Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle. J. Appl.Physiol. 81(5): 2142-2146, 1996.We investigatedthe cardiovascular responses to acute hypercapnia during the menstrualcycle. Eleven female subjects with regular menstrual cycles performedhypercapnic rebreathing tests during the follicular and luteal phasesof their menstrual cycles. Ventilatory and cardiovascular variableswere recorded breath by breath. Serum progesterone and estradiol weremeasured on each occasion. Serum progesterone was higher during theluteal [50.4 ± 9.6 (SE) nmol/l] than during thefollicular phase (2.1 ± 0.7 nmol/l;P < 0.001), but serum estradiol didnot differ (follicular phase, 324 ± 101 pmol/l; luteal phase, 162 ± 71 pmol/l; P = 0.61). Thesystolic blood pressure responses during hypercapnia were 2.0 ± 0.3 and 4.0 ± 0.5 mmHg/Torr (1 Torr = 1 mmHg rise inend-tidal PCO₂) during the follicularand luteal phases, respectively, of the menstrual cycle(P < 0.01). The diastolic bloodpressure responses were 1.1 ± 0.2 and 2.1 ± 0.3 mmHg/Torrduring the follicular and luteal phases, respectively(P < 0.002). Heart rate responses did not differ during the luteal (1.7 ± 0.3 beats ^· min^{1 ·} Torr¹)and follicular phases (1.4 ± 0.3 beats ^· min^{1 ·} Torr¹;P = 0.59). These data demonstrate agreater pressor response during the luteal phase of the menstrual cyclethat may be related to higher serum progesterone concentrations.

     

Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs

Brändle, Marian, Kaushik P. Patel, Wei Wang, andIrving H. Zucker. Hemodynamic and norepinephrine responses topacing-induced heart failure in conscious sinoaortic-denervated dogs.J. Appl. Physiol. 81(4):1855-1862, 1996.The present study was undertaken to determinethe effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations thatoccur in the pacing-induced model of congestive heart failure. Twogroups of dogs were examined: intact(n = 9) and SAD(n = 9). Both groups of dogs werestudied in the control (prepace) state and each week after theinitiation of ventricular pacing at 250 beats/min. After the pacemakerwas turned off, hemodynamic and plasma norepinephrine levels returnedtoward control levels in the prepaced state and after 1 and 2 wk ofpacing. However, by 3 wk all hemodynamic and norepinephrine levelsremained relatively constant over the 10-min observation period withthe pacemaker off. With the pacemaker off, left ventricularend-diastolic pressure went from 2.7 ± 1.4 (SE) mmHg during theprepace state to 23.2 ± 2.9 mmHg in the heart failure state inintact dogs (P < 0.01). Leftventricular end-diastolic pressure increased to 27.1 ± 2.2 mmHgfrom a control level of 4.2 ± 1.9 mmHg in SAD dogs(P < 0.0003). Mean arterial pressuresignificantly decreased in intact and SAD dogs. Resting heart rate wassignificantly higher in SAD dogs and increased to 135.8 ± 8.9 beats/min in intact dogs and 136.1 ± 6.5 beats/min in SAD dogs.There were no significant differences in the hemodynamic parametersbetween intact and SAD dogs after pacing. Plasma norepinephrine wassignificantly lower in intact than in SAD dogs before pacing (197.7 ± 21.6 vs. 320.6 ± 26.6 pg/ml;P < 0.005). In the heart failurestate, plasma norepinephrine increased significantly in both intact(598.3 ± 44.2 pg/ml) and SAD (644.0 ± 64.6 pg/ml) groups. Therewere no differences in the severity or the magnitude of the developedheart failure state in SAD vs. intact dogs. We conclude from these datathat the arterial baroreflex is not the sole mechanism for the increasein sympathetic drive in heart failure.

     

Muscle fatigue and exhaustion during dynamic leg exercise in normoxia and hypobaric hypoxia

Fulco, Charles S., Steven F. Lewis, Peter N. Frykman, RobertBoushel, Sinclair Smith, Everett A. Harman, Allen Cymerman, and Kent B. Pandolf. Muscle fatigue and exhaustion during dynamic leg exercisein normoxia and hypobaric hypoxia. J. Appl. Physiol. 81(5): 1891-1900, 1996.Using anexercise device that integrates maximal voluntary static contraction(MVC) of knee extensor muscles with dynamic knee extension, we comparedprogressive muscle fatigue, i.e., rate of decline in force-generatingcapacity, in normoxia (758 Torr) and hypobaric hypoxia (464 Torr).Eight healthy men performed exhaustive constant work rate kneeextension (21 ± 3 W, 79 ± 2 and 87 ± 2% of 1-leg kneeextension O₂ peak uptake fornormoxia and hypobaria, respectively) from knee angles of90-150° at a rate of 1 Hz. MVC (90° knee angle) wasperformed before dynamic exercise and during 5-s pauses every 2 minof dynamic exercise. MVC force was 578 ± 29 N in normoxia and 569 ± 29 N in hypobaria before exercise and fell, at exhaustion, to similar levels (265 ± 10 and 284 ± 20 N for normoxia andhypobaria, respectively; P > 0.05)that were higher (P < 0.01) thanpeak force of constant work rate knee extension (98 ± 10 N, 18 ± 3% of MVC). Time to exhaustion was 56% shorter for hypobariathan for normoxia (19 ± 5 vs. 43 ± 7 min, respectively;P < 0.01), and rate of right leg MVC fall wasnearly twofold greater for hypobaria than for normoxia (mean slope = 22.3 vs. 11.9 N/min, respectively;P < 0.05). With increasing durationof dynamic exercise for normoxia and hypobaria, integratedelectromyographic activity during MVC fell progressively with MVCforce, implying attenuated maximal muscle excitation. Exhaustion, perse, was postulated to relate more closely to impaired shorteningvelocity than to failure of force-generating capacity.

     

Supraglottic airway pressure-flow relationships during oronasal airflow partitioning in dogs

Amis, T. C., N. O'Neill, T. Van der Touw, A. Tully, and A. Brancatisano. Supraglottic airway pressure-flow relationships during oronasal airflow partitioning in dogs. J. Appl.Physiol. 81(5): 1958-1964, 1996.We studiedpressure-flow relationships in the supraglottic airway of eight pronemouth-open anesthetized (intravenous chloralose or pentobarbitalsodium) crossbred dogs (weight 15-26 kg) during increasingrespiratory drive (CO₂administration; n = 4) and duringgraded-voltage electrical stimulation (SV;n = 4) of the soft palate muscles.During increased respiratory drive, inspiratory airflow occurred viaboth the nose (n) and mouth(m), with the ratio of n tom[%(n/m)]decreasing maximally from 16.0 ± 7.0 (SD) to 2.4 ± 1.6%(P < 0.05). Simultaneously, oralairway resistance at peak inspiratory flow decreased from 2.1 ± 1.0 to 0.4 ± 0.4 cmH₂O(P < 0.05), whereas nasal airway resistance did not change (14.4 ± 7.2 to 13.1 ± 5.4 cmH₂O;P = 0.29). Inspiratory pressure-flowplots of the oral airway were inversely curvilinear or more complex innature. Nasal pathway plots, however, demonstrated a positive linearrelationship in all animals (r = 0.87 ± 0.11; all P < 0.001). Duringelectrical stimulation of soft palate muscle contraction accompanied bygraded constant-inspiratory airflows of 45-385 ml/s through anisolated upper airway, %(n/m)decreased from 69 ± 50 to 10 ± 13% at a SV of 84 ± 3% ofmaximal SV (P < 0.001). At a SV of85 ± 1% of maximum, normalized oral airway resistance (expressedas percent baseline) fell to 5 ± 3%, whereas normalized nasalresistance was 80 ± 9% (both P < 0.03). Thus control of oronasal airflow partitioning in dogsappears mediated more by alterations in oral route geometry than byclosure of the nasopharyngeal airway.

     

Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension

Brilli, Richard J., Brian Krafte-Jacobs, Daniel J. Smith,Dominick Roselle, Daniel Passerini, Amos Vromen, Lori Moore, CsabaSzabó, and Andrew L. Salzman. Intratracheal instillation ofa novel NO/nucleophile adduct selectively reduces pulmonary hypertension. J. Appl. Physiol. 83(6):1968-1975, 1997.We examined the pulmonary and systemichemodynamic effects of administering soluble nitric oxide (NO) donorcompounds (NO/nucleophile adducts, i.e., NONOates) directly into thetrachea of animals with experimentally induced pulmonary hypertension.Steady-state pulmonary hypertension was created by using thethromboxane agonist U-46619. Yorkshire pigs were randomly assigned toone of four groups: group 1,intratracheal saline (control; n = 8);group 2, intratracheal sodiumnitroprusside (n = 6);group 3, intratracheal ethylputreanineNONOate (n = 6); andgroup 4, intratracheal2-(dimethylamino)-ethylputreanine NONOate (DMAEP/NO;n = 6). Pulmonary and systemichemodynamics were monitored after drug instillation.Group 4 had significant reductions in pulmonary vascular resistance index (PVRI) at all time points comparedwith steady state and compared with group1 (P < 0.05), whereas systemic vascular resistance index did not change. The meanchange in mean pulmonary arterial pressure in group4 was 33.1 ± 1.2% compared with +6.4 ± 1.3% in group 1 (P < 0.001), and the mean change inmean arterial pressure was 9.3 ± 0.7% compared with acontrol value of 0.9 ± 0.5%(P < 0.05). Groups 2 and 3 hadsignificant decreases in both PVRI and systemic vascular resistanceindex compared with steady state and with group1. In conclusion, intratracheal instillation of apolar-charged tertiary amine NONOate DMAEP/NO results in the selectivereduction of PVRI. Intermittent intratracheal instillation of selectiveNONOates may be an alternative to continuously inhaled NO in thetreatment of pulmonary hypertension.

     

Hemodynamic correlates of effective arterial elastance in mitral stenosis before and after balloon valvotomy

Colin, Patrice, Michel Slama, Alec Vahanian, YvesLecarpentier, Gilbert Motté, and Denis Chemla. Hemodynamiccorrelates of effective arterial elastance in mitral stenosis beforeand after balloon valvotomy. J. Appl.Physiol. 83(4): 1083-1089, 1997.This study hadthe purpose of documenting the hemodynamic correlates of effectivearterial elastance (Ea; i.e., an accurate estimate of hydraulic load)in mitral stenosis (MS) patients. The main hypothesis tested was thatEa relates to the total vascular resistance (R)-to-pulse intervalduration (T) ratio(R/T) in MS patients both before andafter successful balloon mitral valvotomy (BMV). High-fidelity aorticpressure recordings were obtained in 10 patients (40 ± 12 yr)before and 15 min after BMV. Ea value was calculated as the ratio ofthe steady-state end-systolic aortic pressure (ESAP) to stroke volume(thermodilution). Ea increased after BMV (from 1.55 ± 0.63 to 1.83 ± 0.71 mmHg/ml; P < 0.05). Throughout the procedure, there was a strong linearrelationship between Ea and R/T: Ea = 1.09R/T  0.01 mmHg/ml,r = 0.99, P = 0.0001. This ultimately dependedon the powerful link between ESAP and mean aortic pressure [MAP;r = 0.99, 95% confidence interval for the difference (MAP  ESAP) from 18.5 to +4.5 mmHg].Ea was also related to total arterial compliance (area method) and towave reflections (augmentation index), although to a lesser extent. After BMV, enhanced and anticipated wave reflections were observed, andthis was likely to be explained by decreased arterial compliance. Thepresent study indicated that Ea depended mainly on the steady componentof hydraulic load (i.e., R) and on heart period (i.e., T) in MS patients.