Reflex cardiovascular responses evoked by selective activation of skeletal muscle ergoreceptors

It is well known that theexercise pressor reflex (EPR) is mediated by group III and IV skeletalmuscle afferent fibers, which exhibit unique discharge responses tomechanical and chemical stimuli. Based on the difference in dischargepatterns of group III and IV muscle afferents, we hypothesized thatactivation of mechanically sensitive (MS) fibers would evoke adifferent pattern of cardiovascular responses compared with activationof both MS and chemosensitive (CS) fibers. Experiments were conductedin chloralose-urethane-anesthetized cats (n = 10).Passive muscle stretch was used to activate MS afferents, andelectrically evoked contraction of the triceps surae was used toactivate both MS and CS muscle afferents. No significant differenceswere shown in reflex heart rate and mean arterial pressure (MAP)responses between passive muscle stretch and evoked muscle contraction. However, when the reflex responses were matched according totension-time index (TTI), the peak MAP response (67 ± 4 vs.56 ± 4 mmHg, P < 0.05) was significantly greaterat higher TTI (427 ± 18 vs. 304 ± 13 kg · s, highvs. low TTI, P < 0.05), despite different modes ofafferent fiber activation. When the same mode of afferent fiberactivation was compared, the peak MAP response (65 ± 7 vs. 55 ± 5 mmHg, P < 0.05) was again predicted bythe magnitude of TTI (422 ± 24 vs. 298 ± 19 kg · s,high vs. low TTI, P < 0.05). Total sensory input fromskeletal muscle ergoreceptors, as predicted by TTI and not the modalityof afferent fiber activation (muscle contraction vs. passive stretch),is suggested to be the primary determinant of the magnitude of theEPR-evoked cardiovascular response.

     

Effect of sleep/wake state on arterial blood pressure in genetically identical mice

Genetic determinants may contribute to the large variability inarterial blood pressure responses to changes in sleep/wake state inhumans. In this study, we developed techniques to examine therelationship between sleep/wake state and mean arterial pressure (MAP)in unrestrained, genetically identical mice (C57BL/6J;n = 9). The left common carotid arterywas catheterized, and arterial blood gases were analyzed 24-48 hpostsurgery to verify normal respiratory and metabolic function. Theanimals were then allowed to cycle naturally through sleep/wake statesover a 3- to 4-h period while continuous polysomnography and arterialpressure measurements were made. The MAP decreased fromquiet wakefulness to non-rapid-eye-movement sleep (9.8 ± 1.3 mmHg;P < 0.001) and further decreasedfrom non-rapid-eye-movement to rapid-eye-movement sleep (9.7 ± 1.8 mmHg; P < 0.001). We conclude thatthe inbred strain of C57BL/6J mice exhibits significant and consistentchanges in MAP related to sleep/wake state. Future studies can compare responses in this strain of mice with those in other inbred or transgenic mice to determine whether specific genes regulate arterial blood pressure responses to sleep/wake state.

     

Subnormal norepinephrine release relates to presyncope in astronauts after spaceflight

Fritsch-Yelle, Janice M., Peggy A. Whitson, Roberta L. Bondar, and Troy E. Brown. Subnormal norepinephrine release relates to presyncope in astronauts after spaceflight.J. Appl. Physiol. 81(5):2134-2141, 1996.Postflight orthostatic intolerance isexperienced by virtually all astronauts but differs greatly in degreeof severity. We studied cardiovascular responses to upright posture in40 astronauts before and after spaceflights lasting up to 16 days. Weseparated individuals according to their ability to remain standingwithout assistance for 10 min on landing day. Astronauts who could notremain standing on landing day had significantly smaller increases inplasma norepinephrine levels with standing than did those who couldremain standing (105 ± 41 vs. 340 ± 62 pg/ml;P = 0.05). In addition, they hadsignificantly lower standing peripheral vascular resistance (23 ± 3 vs. 34 ± 3 mmHg ^· l^{1 ·} min;P = 0.02) and greater decreases insystolic (28 ± 4 vs. 11 ± 3 mmHg;P = 0.002) and diastolic (14 ± 7 vs. 3 ± 2 mmHg; P = 0.0003) pressures. The presyncopal group also hadsignificantly lower supine (16 ± 1 vs. 21 ± 2 mmHg ^· l^{1 ·} min;P = 0.04) and standing (23 ± 2 vs.32 ± 2 mmHg ^· l^{1 ·} min;P = 0.038) vascular resistance, supine(66 ± 2 vs. 73 ± 2 mmHg; P = 0.008) and standing (69 ± 4 vs. 77 ± 2 mmHg;P = 0.007) diastolic pressure, andsupine (109 ± 3 vs. 114 ± 2 mmHg; P = 0.05) and standing (99 ± 4 vs. 108 ± 3 mmHg; P = 0.006) systolic pressures before flight. This is the first study toclearly document these differences among presyncopal and nonpresyncopalastronauts after spaceflight and also offer the possibility ofpreflight prediction of postflight susceptibility. These resultsclearly point to hypoadrenergic responsiveness, possibly centrallymediated, as a contributing factor in postflight orthostaticintolerance. They may provide insights into autonomic dysfunction inEarthbound patients.

     

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.

     

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.

     

Intracerebroventricular propranolol prevented vascular resistance increases on arousal from sleep apnea

Zinkovska, Sophia, and Debra A. Kirby.Intracerebroventricular propranolol prevented vascular resistanceincreases on arousal from sleep apnea. J. Appl.Physiol. 82(5): 1637-1643, 1997.Despite theincreased risk of sudden cardiac death associated with sleep apnea,little is known about mechanisms controlling cardiovascular responsesto sleep apnea and arousal. Chronically instrumented pigs were used toinvestigate the effects of airway obstruction (AO) duringrapid-eye-movement (REM) and non-REM (NREM) sleep and arousal on meanarterial pressure (MAP), heart rate (HR), cardiac output (CO), andtotal peripheral resistance (TPR). A stainless steelcannula was implanted in the lateral cerebral ventricle. During REMsleep, HR was 133 ± 10 beats/min, MAP was 65 ± 3 mmHg, CO was1,435 ± 69 ml/min, and TPR was 0.046 ± 0.004 mmHg · ml¹ · min.During AO, CO decreased by 90 ± 17 ml/min(P < 0.05). On arousal from AO, MAPincreased by 15 ± 3 mmHg, HR increased by 10 ± 3 beats/min, andTPR increased by 0.008 ± 0.001 mmHg · ml¹ · min(all P < 0.05). Changes during NREMwere similar but were more modest during AO. After theintracerebroventricular administration of propranolol (50 µg/kg; a-adrenoreceptor blocking agent), decreases in CO during AO andincreases in HR during arousal were intact, but increases in MAP andTPR were no longer significant. These data suggest thatvascular responses to AO during sleep may be regulated in part by-adrenergic receptors in the central nervous system.

     

Deterioration of cerebral autoregulation during orthostatic stress: insights from the frequency domain

To determine whether dynamiccerebral autoregulation is impaired during orthostatic stress, cerebralblood flow (CBF) velocity in the middle cerebral artery (transcranialDoppler) and mean arterial pressure (MAP; Finapres) were measuredcontinuously in 12 healthy subjects during ramped maximal lower bodynegative pressure (LBNP) to presyncope. Velocity andpressure were averaged over 6-min periods of stable data at rest andduring LBNP to examine steady-state cerebral hemodynamics. Beat-to-beatvariability of velocity and pressure were quantified by a "variationindex" (oscillatory amplitude/steady-state mean value) and by powerspectral analysis. The dynamic relationship between changes in pressureand velocity was evaluated by the estimates of transfer and coherencefunction. The results of the study were as follows.Steady-state MAP remained relatively constant during LBNP, whereas CBFvelocity decreased progressively by 6, 15, and 21% at 30,40, and 50 mmHg LBNP, respectively(P < 0.05 compared withbaseline). At the maximal level of LBNP (30 s beforepresyncope) MAP decreased by 9.4% in association with a prominentreduction in velocity by 24% (P < 0.05 compared with baseline). The variation index of pressure increasedsignificantly from 3.8 ± 0.3% at baseline to 4.5 ± 0.6% at50 mmHg LBNP in association with an increase in the variation index of velocity from 6.0 ± 0.6 to 8.4 ± 0.7%(P < 0.05). Consistently, the low-(0.07-0.20 Hz) and high-frequency (0.20-0.30 Hz) power ofvariations in pressure and velocity increased significantly at highlevels of LBNP (P < 0.05) inassociation with an increase in transfer function gain (24% at50 mmHg, P < 0.05). We conclude that the damping effects ofautoregulation on variations in CBF velocity are diminishedduring orthostatic stress in association with substantial falls insteady-state CBF velocity. We suggest that these changes may contributein part to the development of presyncope.

     

Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure

To elucidate thetime course of sympathovagal balance and its relationship to leftventricular function in heart failure, we serially evaluated leftventricular contractility and relaxation and autonomic tone in 11 conscious dogs with tachycardia-induced heart failure. We determined adynamic map of sympathetic and parasympathetic modulation by powerspectral analysis of heart rate variability. The left ventricular peak+dP/dt substantially fell from 3,364 ± 338 to 1,959 ± 318 mmHg/s (P < 0.05) on the third day and declined gradually to 1,783 ± 312 mmHg/s at 2 wk of rapid ventricular pacing. In contrast, the timeconstant of left ventricular pressure decay and end-diastolic pressureincreased gradually from 25 ± 4 to 47 ± 5 ms(P < 0.05) and from 10 ± 2 to21 ± 3 mmHg (P < 0.05), respectively, at 2 wk of pacing. The high-frequency component(0.15-1.0 Hz), a marker of parasympathetic modulation, decreasedfrom 1,928 ± 1,914 to 62 ± 68 × 10³ms²(P < 0.05) on the third day andfurther to 9 ± 12 × 10³ms²(P < 0.05) at 2 wk. Similar to thetime course of left ventricular diastolic dysfunction, plasmanorepinephrine levels and the ratio of low (0.05- to 0.15-Hz)- tohigh-frequency component increased progressively from 135 ± 50 to 532 ± 186 pg/ml (P < 0.05) and from 0.06 ± 0.06 to 1.12 ± 1.01 (P < 0.05), respectively, at 2 wk ofpacing. These cardiac and autonomic dysfunctions recovered graduallytoward the normal values at 2 wk after cessation of pacing. Thus aparallel decline in left ventricular contractility with parasympatheticinfluence and a parallel progression in left ventricular diastolicdysfunction with sympathoexcitation suggest a close relationshipbetween cardiac dysfunction and autonomic dysregulation duringdevelopment of heart failure.

     

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.

     

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.

     

Changes in agonist-antagonist EMG, muscle CSA, and force during strength training in middle-aged and older people

Effects of 6 mo of heavy-resistance trainingcombined with explosive exercises on neural activation of the agonistand antagonist leg extensors, muscle cross-sectional area (CSA) of thequadriceps femoris, as well as maximal and explosive strength wereexamined in 10 middle-aged men (M40; 42 ± 2 yr), 11 middle-agedwomen (W40; 39 ± 3 yr), 11 elderly men (M70; 72 ± 3 yr) and 10 elderly women (W70; 67 ± 3 yr). Maximal andexplosive strength remained unaltered during a 1-mo control period withno strength training. After the 6 mo of training, maximal isometric anddynamic leg-extension strength increased by 36 ± 4 and 22 ± 2%(P < 0.001) in M40, by 36 ± 3 and 21 ± 3% (P < 0.001) in M70,by 66 ± 9 and 34 ± 4% (P < 0.001) in W40, and by 57 ± 10 and 30 ± 3%(P < 0.001) in W70, respectively.All groups showed large increases (P < 0.05-0.001) in the maximum integrated EMGs (iEMGs) of theagonist vastus lateralis and medialis. Significant(P < 0.05-0.001) increasesoccurred in the maximal rate of isometric force productionand in a squat jump that were accompanied with increased(P < 0.05-0.01) iEMGs of theleg extensors. The iEMG of the antagonist biceps femoris muscle duringthe maximal isometric leg extension decreased in both M70 (from 24 ± 6 to 21 ± 6%; P < 0.05)and in W70 (from 31 ± 9 to 24 ± 4%;P < 0.05) to the same level asrecorded for M40 and W40. The CSA of the quadriceps femoris increasedin M40 by 5% (P < 0.05), in W40 by9% (P < 0.01), in W70 by 6%(P < 0.05), and in M70 by 2% (notsignificant). Great training-induced gains in maximal and explosivestrength in both middle-aged and elderly subjects were accompanied bylarge increases in the voluntary activation of the agonists, withsignificant reductions in the antagonist coactivation in the elderlysubjects. Because the enlargements in the muscle CSAs in bothmiddle-aged and elderly subjects were much smaller in magnitude, neuraladaptations seem to play a greater role in explaining strength andpower gains during the present strength-training protocol.

     

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.

     

Enhanced brain natriuretic peptide response to peak exercise in heart transplant recipients

We investigatedthe atrial (ANP) and brain natriuretic peptides (BNP), catecholamines,heart rate, and blood pressure responses to graded upright maximalcycling exercise of eight matched healthy subjects andcardiac-denervated heart transplant recipients (HTR). Baseline heart rate and diastolic blood pressure, together with ANP(15.2 ± 3.7 vs. 4.4 ± 0.8 pmol/l;P < 0.01) and BNP (14.3 ± 2.6 vs. 7.4 ± 0.6 pmol/l; P < 0.01), were elevated in HTR, but catecholamine levels were similarin both groups. Peak exercise O₂uptake and heart rate were lower in HTR. Exercise-inducedmaximal ANP increase was similar in both groups (167 ± 34 vs. 216 ± 47%). Enhanced BNP increase was significant only in HTR (37 ± 8 vs. 16 ± 8%; P < 0.05).Similar norepinephrine but lower peak epinephrine levels were observedin HTR. ANP and heart rate changes from rest to 75% peak exercise werenegatively correlated (r = 0.76, P < 0.05),and BNP increase was correlated with left ventricular mass index(r = 0.83, P < 0.01) after hearttransplantation. Although ANP increase was notexaggerated, these data support the idea that the chronotropiclimitation secondary to sinus node denervation might stimulate ANPrelease during early exercise in HTR. Furthermore, the BNPresponse to maximal exercise, which is related to the left ventricularmass index of HTR, is enhanced after heart transplantation.

     

Contribution of abdomen and legs to central blood volume expansion in humans during immersion

Johansen, Lars Bo, Thomas Ulrik Skram Jensen, Bettina Pump,and Peter Norsk. Contribution of abdomen and legs to central bloodvolume expansion in humans during immersion. J. Appl.Physiol. 83(3): 695-699, 1997.The hypothesis wastested that the abdominal area constitutes an important reservoir forcentral blood volume expansion (CBVE) during water immersion inhumans. Six men underwent 1) water immersion for 30 min (WI),2) water immersion for 30 min withthigh cuff inflation (250 mmHg) during initial 15 min to exclude legsfrom contributing to CBVE (WI+Occl), and3) a seated nonimmersed control with15 min of thigh cuff inflation (Occl). Plasma protein concentration andhematocrit decreased from 68 ± 1 to 64 ± 1 g/l and from 46.7 ± 0.3 to 45.5 ± 0.4%(P < 0.05), respectively, during WIbut were unchanged during WI+Occl. Left atrial diameter increased from27 ± 2 to 36 ± 1 mm (P < 0.05) during WI and increased similarly during WI+Occl from 27 ± 2 to 35 ± 1 mm (P < 0.05). Centralvenous pressure increased from 3.7 ± 1.0 to 10.4 ± 0.8 mmHg during WI (P < 0.05) butonly increased to 7.0 ± 0.8 mmHg during WI+Occl(P < 0.05). In conclusion, the dilution of blood induced by WI to the neck is caused by fluid from thelegs, whereas the CBVE is caused mainly by blood from theabdomen.

     

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.

     

Forearm training reduces the exercise pressor reflex during ischemic rhythmic handgrip

Mostoufi-Moab, Sogol, Eric J. Widmaier, Jacob A. Cornett,Kristen Gray, and Lawrence I. Sinoway. Forearm training reduces the exercise pressor reflex during ischemic rhythmic handgrip. J. Appl. Physiol. 84(1): 277-283, 1998.We examined the effects of unilateral, nondominant forearmtraining (4 wk) on blood pressure and forearm metabolites duringischemic and nonischemic rhythmic handgrip (30 1-s contractions/min at25% maximal voluntary contraction). Contractions were performed by 10 subjects with the forearm enclosed in a pressurized Plexiglas tank toinduce ischemic conditions. Training increased the endurance time inthe nondominant arm by 102% (protocol1). In protocol 2,tank pressure was increased in increments of 10 mmHg/min to +50 mmHg.Training raised the positive-pressure threshold necessary to engage thepressor response. In protocol 3,handgrip was performed at +50 mmHg and venous blood samples wereanalyzed. Training attenuated mean arterial pressure (109 ± 5 and98 ± 4 mmHg pre- and posttraining, respectively, P < 0.01), venous lactate (2.9 ± 0.4 and 1.8 ± 0.3 mmol/l pre- and posttraining, respectively,P < 0.01), and the pH response (7.21 ± 0.02 and 7.25 ± 0.01, pre- and posttraining, respectively, P < 0.01). However, deep venousO₂ saturation was unchanged.Training increased the positive-pressure threshold for metaboreceptorengagement, reduced metabolite concentrations, and reduced meanarterial pressure during ischemic exercise.

     

Head-down-tilt bed rest alters forearm vasodilator and vasoconstrictor responses

To test thehypothesis that head-down-tilt bed rest (HDBR) for 14 days altersvascular reactivity to vasodilatory and vasoconstrictor stimuli, thereactive hyperemic forearm blood flow (RHBF, measured by venousocclusion plethysmography) and mean arterial pressure (MAP, measured byFinapres) responses after 10 min of circulatory arrest were measured ina control trial (n = 20) and whensympathetic discharge was increased by a cold pressor test (RHBF + coldpressor test; n = 10). Vascularconductance (VC) was calculated (VC = RHBF/MAP). In the control trial,peak RHBF at 5 s after circulatory arrest (34.1 ± 2.5 vs.48.9 ± 4.3 ml · 100 ml¹ · min¹)and VC (0.34 ± 0.02 vs. 0.53 ± 0.05 ml · 100 ml¹ · min¹ · mmHg¹)were reduced in the post- compared with the pre-HDBR tests(P < 0.05). Total excess RHBF over 3 min was diminished in the post- compared with the pre-HDBR trial (84.8 vs. 117 ml/100 ml, P < 0.002). Theability of the cold pressor test to lower forearm blood flow was lessin the post- than in the pre-HDBR test(P < 0.05), despite similarincreases in MAP. These data suggest that regulation of vasculardilation and the interaction between dilatory and constrictorinfluences were altered with bed rest.

     

Brain natriuretic peptide inhibits hypoxic pulmonary hypertension in rats

Brainnatriuretic peptide (BNP) is a pulmonary vasodilator that is elevatedin the right heart and plasma of hypoxia-adapted rats. To test thehypothesis that BNP protects against hypoxic pulmonary hypertension, wemeasured right ventricular systolic pressure (RVSP), right ventricle(RV) weight-to-body weight (BW) ratio (RV/BW), and percentmuscularization of peripheral pulmonary vessels (%MPPV) in rats givenan intravenous infusion of BNP, atrial natriuretic peptide (ANP), orsaline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm).Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPVthan did normoxic controls. Under normoxic conditions, BNP infusion(0.2 and 1.4 µg/h) increased plasma BNP but had no effect on RVSP,RV/BW, or %MPPV. Under hypoxic conditions, low-rate BNP infusion (0.2 µg/h) had no effect on plasma BNP or on severity of pulmonaryhypertension. However, high-rate BNP infusion (1.4 µg/h) increasedplasma BNP (69 ± 8 vs. 35 ± 4 pg/ml, P < 0.05),lowered RV/BW (0.87 ± 0.05 vs. 1.02 ± 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%,P < 0.05). There was also a trend towardlower RVSP (55 ± 3 vs. 64 ± 2, P = not significant).Infusion of ANP at 1.4 µg/h increased plasma ANP in hypoxic rats (759 ± 153 vs. 393 ± 54 pg/ml, P < 0.05) but had noeffect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulatepulmonary vascular responses to hypoxia and, at the doses used in thisstudy, is more effective than ANP at blunting pulmonary hypertensionduring the first 2 wk of hypoxia.

     

Muscular blood flow response to submaximal leg exercise in normal subjects and in patients with heart failure

Isnard, Richard, Philippe Lechat, Hanna Kalotka, HafidaChikr, Serge Fitoussi, Joseph Salloum, Jean-Louis Golmard, Daniel Thomas, and Michel Komajda. Muscular blood flow response to submaximal leg exercise in normal subjects and in patients with heartfailure. J. Appl. Physiol. 81(6):2571-2579, 1996.Blood flow to working skeletal muscle is usuallyreduced during exercise in patients with congestive heart failure. Anintrinsic impairment of skeletal muscle vasodilatory capacity has beensuspected as a mechanism of this muscle underperfusion during maximalexercise, but its role during submaximal exercise remains unclear.Therefore, we studied by transcutaneous Doppler ultrasonography thearterial blood flow in the common femoral artery at rest and during asubmaximal bicycle exercise in 12 normal subjects and in 30 patientswith heart failure. Leg blood flow was lower in patientsthan in control subjects at rest [0.29 ± 0.14 (SD) vs. 0.45 ± 0.14 l/min, P < 0.01], at absolute powers and at the same relative power (2.17 ± 1.06 vs. 4.39 ± 1.4 l/min, P < 0.001). Because mean arterial pressure was maintained, leg vascularresistance was higher in patients than in control subjects at rest (407 ± 187 vs. 247 ± 71 mmHg ^· l^{1 ·} min,P < 0.01) and at thesame relative power (73 ± 49 vs. 31 ± 13 mmHg ^· l^{1 ·} min,P < 0.01) but not at absolutepowers. Although the magnitude of increase in leg blood flow correctedfor power was similar in both groups (31 ± 10 vs. 34 ± 10 ml ^· min^{1 ·} W¹),the magnitude of decrease of leg vascular resistance corrected forpower was higher in patients than in control subjects (5.9 ± 3.3 vs. 1.9 ± 0.94 mmHg ^· l^{1 ·} min ^· W¹,P < 0.001). These results suggestthat the ability of skeletal muscle vascular resistance to decrease isnot impaired and that intrinsic vascular abnormalities do not limitvasodilator response to submaximal exercise in patients with heartfailure.

     

Sympathetic withdrawal and forearm vasodilation during vasovagal syncope in humans

Dietz, Niki M., John R. Halliwill, John M. Spielmann, LoriA. Lawler, Bettina G. Papouchado, Tamara J. Eickhoff, and Michael J. Joyner. Sympathetic withdrawal and forearm vasodilation duringvasovagal syncope in humans. J. Appl.Physiol. 82(6): 1785-1793, 1997.Our aim was todetermine whether sympathetic withdrawal alone can account for theprofound forearm vasodilation that occurs during syncope in humans. Wealso determined whether either vasodilating ₂-adrenergic receptors ornitric oxide (NO) contributes to this dilation. Forearm blood flow wasmeasured bilaterally in healthy volunteers(n = 10) by using plethysmographyduring two bouts of graded lower body negative pressure (LBNP) tosyncope. In one forearm, drugs were infused via a brachial arterycatheter while the other forearm served as a control. In the controlarm, forearm vascular resistance (FVR) increased from 77 ± 7 unitsat baseline to 191 ± 36 units with 40 mmHg of LBNP(P < 0.05). Mean arterial pressurefell from 94 ± 2 to 47 ± 4 mmHg just before syncope, and allsubjects demonstrated sudden bradycardia at the time of syncope. At theonset of syncope, there was sudden vasodilation and FVR fell to 26 ± 6 units (P < 0.05 vs. baseline). When the experimental forearm was treated withbretylium, phentolamine, and propranolol, baseline FVR fell to 26 ± 2 units, the vasoconstriction during LBNP was absent, and FVR fellfurther to 16 ± 1 units at syncope(P < 0.05 vs. baseline). During thesecond trial of LBNP, mean arterial pressure again fell to 47 ± 4 mmHg and bradycardia was again observed. Treatment of the experimentalforearm with the NO synthase inhibitorN^G-monomethyl-L-arginine in additionto bretylium, phentolamine, and propranolol significantly increasedbaseline FVR to 65 ± 5 units but did not prevent the marked forearmvasodilation during syncope (FVR = 24 ± 4 vs. 29 ± 8 units inthe control forearm). These data suggest that the profound vasodilationobserved in the human forearm during syncope is not mediated solely bysympathetic withdrawal and also suggest that neither₂-adrenergic-receptor-mediated vasodilation nor NO is essential to observe this response.