Respiratory and baroreceptor reflex interactions in man.

Respiratory and arterial baroreceptor reflex interactions were studied in six healthy young adults. Carotid baroreceptors were stimulated with two intensities of neck suction during early inspiration or expiration at 100 or 150% of each subject's normal tidal volume. Sinus node responses to moderate baroreflex stimuli were inhibited by inspiration, but responses to intense stimuli were not influenced by the phase of respiration. Supranormal tidal volume did not diminish responses to inspiratory baroreflex stimuli, but significantly reduced responses to expiratory stimuli. These results provide evidence for a central respiratory baroreceptor reflex interaction in man whose quality is dependent upon the level of afferent baroreceptor activity and the depth of inspiration.

Alterations in the baroreceptor reflex in conscious dogs with heart failure.

The effectiveness of the baroreceptor reflex in conscious dogs with experimental cardiac hypertrophy and heart failure was compared with that in a group of normal conscious dogs. Cardiac hypertrophy and heart failure were produced by tricuspid avulsion and progressive pulmonary stenosis. The sensitivity of the baroreceptor reflex to transient hypertension was assessed by determining the slope of the regression line relating the prolongation of the R-R interval to the rise in systolic arterial pressure during the transient elevation of arterial pressure induced by an intravenous injection of 1-phenylephrine. The mean slope averaged 22.4+/-2.3 msec/nm Hg in 16 normal animals. 23.1 +/-1.5 in five sham-operated animals, and was significantly reduced to 8.3 +/-0.8 in 10 dogs with hypertrophy alone (P < 0.001), and to 3.3+/-0.5 in nine dogs with heart failure (P < 0.001). The response to baroreceptor hypotension was compared during bilateral carotid artery occlusion (BCO) in six normal and six heart failure dogs previously instrumented with Doppler flow transducers on the superior mesenteric and renal arteries. During BCO, in normal dogs arterial pressure increased 52+/-4 mm Hg, heart rate 33+/-2 beats/min, mesenteric resistance 0.17+/-0.03 mm Hg/ml per min, and renal resistance 0.37+/-0.10 mm Hg/ml per min. In the heart failure group all of these variables increased significantly less (P < 0.01); arterial pressure rose 25 +/-3 mm Hg, heart rate 13 +/-4 beats/min, mesenteric resistance 0.04+/-0.007 mm Hg/ml per min, and renal resistance 0.18+/-0.09 mm Hg/ml per min.Thus, in heart failure, all measured systemic and regional circulatory adjustments consequent to baroreceptor hypo- and hypertension are markedly attenuated. This study demonstrates a profound derangement of a major cardiovascular control mechanism in experimental heart failure.

Mechanisms mediating bradycardia during coronary arteriography.

Cardiac slowing occurring during diagnostic coronary arteriography was studied in 78 patients. Comparable degrees of slowing occurred with injections into the right and into the left coronary arteries into the contralateral artery, and with injections into the coronary artery giving rise to the sinus node artery and into the contralateral artery. Rapid intracoronary injections of isosmotic dextrose solution produced significantly less slowing than comparable injections of contrast medium. Slow injections of contrast medium produced cardiac slowing comparable to that caused by rapid injections of contrast medium. However, the cardiac slowing was significantly greater than that produced by rapid injections of dextrose solution. Inhalation of 100% oxygen did not alter the heart rate response to injections of contrast medium. Atropine produced dose-related attenuation of cardiac slowing. Bradycardia persisting after cholinergic blockade was significantly greater after injections into the coronary artery supplying the sinus node than it was after injections into the contralateral artery. Coronary arteriography produced transient, occasionally profound, arterial hypotension in 38 of 41 patients in whom arterial pressures were recorded. Arterial pressure did not change in three patients. This study suggests that the cardiac slowing which occurs during coronary arteriography in man is due primarily to a cholinergic reflex which may be a human counterpart of the Bezold-Jarisch reflex, observed heretofore only in experimental animals. This slowing appears to be mediated primarily by receptors sensitive to contrast medium, rather than by changes of coronary artery pressure, and secondarily, by direct depression of sinus node function by contrast medium.

Baroreflex control of plasma norepinephrine and heart period in healthy subjects and diabetic patients.

Resting diabetic patients may have excessively rapid heart rates, reduced heart rate variability, and subnormal plasma catecholamine levels. Although all of these abnormalities may relate in some way to baroreceptor reflex function, there have been surprisingly few attempts to evaluate systematically baroreflex mechanisms in diabetic patients. Accordingly, we studied autonomic responses over a range of pharmacologically induced arterial pressure changes in 10 unselected young adult insulin-dependent diabetic patients who had no symptoms of autonomic neuropathy, and 12 age-matched nondiabetic subjects. Sympathetic responses were estimated from antecubital vein plasma norepinephrine levels, and parasympathetic responses were estimated from electrocardiographic R-R intervals and their variability (standard deviation). Both were correlated with other noninvasive indexes of peripheral and central nervous system function. Multiple derangements of baroreflex function were found in the diabetic patients studied. Sympathetic abnormalities included subnormal baseline norepinephrine levels, virtual absence of changes of norepinephrine levels during changes of arterial pressure, and supranormal pressor responses to phenylephrine infusions. Parasympathetic abnormalities included subnormal baseline standard deviations of R-R intervals, and R-R interval prolongations during elevations of arterial pressure which were unmistakably present, but subnormal. Our data suggest that in diabetic patients, subnormal baseline plasma norepinephrine levels may signify profound, possibly structural defects of sympathetic pathways. Subnormal resting levels of respiratory sinus arrhythmia may have different implications, however, since vagal, unlike sympathetic reflex abnormalities, can be reversed partly by arterial pressure elevations.

Autonomic pathophysiology in heart failure patients. Sympathetic-cholinergic interrelations.

We conducted this study in an effort to characterize and understand vagal abnormalities in heart failure patients whose sympathetic activity is known. We measured sympathetic (peroneal nerve muscle sympathetic recordings and antecubital vein plasma norepinephrine levels) and vagal (R-R intervals and their standard deviations) activities in eight heart failure patients and eight age-matched healthy volunteers, before and after parasympathomimetic and parasympatholytic intravenous doses of atropine sulfate. At rest, sympathetic and parasympathetic outflows were related reciprocally: heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows. Low dose atropine, which is known to increase the activity of central vagal-cardiac motoneurons, significantly increased R-R intervals in healthy subjects, but did not alter R-R intervals in heart failure patients. Thus, our data document reciprocal supranormal sympathetic and subnormal parasympathetic outflows in heart failure patients and suggest that these abnormalities result in part from abnormalities within the central nervous system.

Sympathetic neural responses to induced ventricular tachycardia.

Although sympathetic mechanisms play a major role in buffering abrupt arterial pressure reductions, including those that occur during tachyarrhythmias, human sympathetic nervous system responses to ventricular tachycardia have not been measured. Muscle sympathetic nerve activity was recorded directly from the peroneal nerve in 16 patients during diagnostic induction of 19 episodes of sustained monomorphic ventricular tachycardia (average rate 189 beats/min, range 130 to 250). Average systolic and diastolic pressures decreased from 149/78 to 61/49 mm Hg by 10 s and increased toward baseline levels to 88/64 mm Hg by 1 min of ventricular tachycardia. Average sympathetic nerve activity increased by 92% at 10 s in direct proportion to arterial pressure reductions and in inverse proportion to ventricular rate and remained 83% above baseline levels at 1 min. The late recovery of arterial pressure during ventricular tachycardia was related significantly to the magnitude of early sympathetic responses. Sympathetic activity tended to lose its discrete bursting pattern during ventricular tachycardia, and power spectral analysis showed that the large sympathetic peaks at the heart rate frequency present during sinus rhythm are absent during ventricular tachycardia. This study is the first to delineate human sympathetic nervous system responses to ventricular tachycardia. The results suggest that in the patients studied, large early sympathetic surges differed from those that occur during sinus rhythm and contributed to hemodynamic stability during ventricular tachycardia.

Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing.

OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p < 0.05). Although most patients showed a strong inverse relation between arterial pressure and muscle sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction < or = 30%) showed no relation between arterial pressure and sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular rather than dual-chamber pacing may be due in part to increased sympathetic nervous outflow.

Enhancement of sympathetic nerve activity by single premature ventricular beats in humans.

This is the first systematic study of the effects of ventricular premature beats on sympathetic nerve activity in humans. Microneurographic techniques were used to record efferent sympathetic activity from the peroneal nerve, and an intracardiac electrode catheter was used to introduce ventricular premature beats after every 6 to 10 sinus heartbeats. Studies were performed in eight patients, aged 22 to 74 years (mean 57), undergoing cardiac electrophysiologic studies. Three patients did not have apparent heart disease and five had coronary artery disease. During sinus rhythm, 19 to 93% (mean 42%) of heartbeats were followed by a pulse-synchronous burst of sympathetic activity. Provoked ventricular premature beats had obvious effects on this activity. Premature beats with coupling intervals less than 80% of sinus cycle length were consistently followed by a burst of sympathetic activity, and this activity was greater in amplitude, duration and area (all p less than 0.05) than were burst of such activity during sinus rhythm. The magnitude of this burst of activity increased as the coupling interval of the ventricular premature beat decreased (p less than 0.0001). In contrast, postextrasystolic beats were followed by nearly complete neural silence. These effects were seen in all patients regardless of baseline burst incidence and the presence or absence of heart disease. Total nerve activity per 10 heartbeats was 6,520 +/- 770 U during ventricular extrastimulation and 5,720 +/- 440 U during normal sinus rhythm (difference not significant). It is concluded that single ventricular premature beats provoke fluxes of muscle sympathetic nerve activity in humans, comprising surges of sympathetic activity larger than those occurring during sinus rhythm, followed by neural silence.

Subnormal heart period variability in heart failure: effect of cardiac transplantation.

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients. Mean heart period variability (+/- SEM) was significantly lower (p less than 0.05) in the heart failure groups (22 +/- 3 ms for medicated and 17 +/- 3 ms for nonmedicated) than in the transplant patients (41 +/- 5 ms) or control subjects (58 +/- 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p less than 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation (R2 = 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 +/- 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p less than 0.001). These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.

Arterial baroreflex impairment in patients during acute coronary occlusion.

OBJECTIVES: We tested whether acute coronary occlusion interferes with arterial baroreceptor control of heart rate in humans. BACKGROUND: Subnormal baroreflex sensitivity (BRS) is an important risk indicator for sudden death. Animal research indicates that both chronic myocardial infarction and acute coronary occlusion impair baroreflex modulation of heart rate. METHODS: We measured RR interval prolongation after phenylephrine-induced systolic pressure increases before and during 2-min coronary occlusions in 47 patients (27 men) undergoing clinically indicated single-vessel coronary angioplasty for stenoses in the proximal or midportion of the vessel causing >50% reduction in the arterial diameter, with normal antegrade flow (33 anterior descending, 10 circumflex, 4 right coronary artery). A control group of 11 patients treated for chronic total occlusion of a coronary artery was assessed to evaluate nonspecific changes in baroreflex function during a 2-min balloon inflation in the occluded artery. RESULTS: The BRS decreased from 5.2+/-3.8 (mean+/-SD) to 4.1+/-3.5 ms x mm Hg(-1) (p=0.01) during the coronary occlusion in the 28 patients with preserved arterial baroreceptor control of heart rate-that is, adequate blood pressure responses and correlation coefficients of the slopes both in baseline and during coronary occlusion. The same phenylephrine dose increased systolic pressure less during than before coronary artery occlusion (21+/-21 versus 36+/-16 mm Hg, p < 0.0001), and in 6 patients it failed to prevent systolic pressure reduction during occlusion. Correlation coefficients of the baroreflex regressions decreased from 0.81+/-0.27 to 0.47+/-0.44 (p < 0.0001) during coronary artery occlusion in the 41 patients with adequate systolic pressure rises in both phenylephrine tests, and the association between RR intervals and rising systolic pressures was lost in 13 patients during coronary occlusion. Balloon inflation in a chronic total occlusion of a coronary artery did not cause significant changes in BRS (from 5.3+/-4.0 to 5.2+/-3.7 ms x mm Hg(-1)), correlation coefficient of the slope or phenylephrine-induced pressure rise. CONCLUSIONS: Our study shows that abrupt coronary occlusion impairs baroreflex modulation of vagal and sympathetic nervous outflow in humans.

Effects of angiographic contrast media on sino-atrial nodal function.

Injection of meglumine diatrizoate (Renografin-76) into the selectively perfused sinus node artery of the dog produces bradycardia which is unaltered by autonomic blockade or by changes in sinus node artery pressure. Contrast agents and other hyperosmolar substances prolong the R-R interval in proportion to their osmolarity. Selective injection of contrast media into other cannulated segments of the coronary tree produces no change in heart rate. Transfemoral arteriography, however, produces bradycardia with both right and left coronary injections. Both direct and reflex sinus node depression occur with coronary arteriography in the dog. Direct effects are mediated by hyperosmolarity.

Impedance cardiograms reliably estimate beat-by-beat changes of left ventricular stroke volume in humans.

Linear regression was used to compare stroke volumes calculated from tetrapolar impedance cardiograms and simultaneous left ventriculograms in 14 patients undergoing diagnostic left heart catheterisation. We calculated three to five consecutive stroke volumes from each ventriculogram. Left ventricular stroke volumes estimated by the two methods correlated closely: the correlation coefficients from pairs of data obtained from individual patients ranged between 0.77 and 1.00 (average = 0.91), and the correlation coefficient for pooled data (all pairs from all subjects) was 0.79 (p less than 0.001). Changes in left ventricular stroke volume measured with the two methods also correlated well (r = 0.89 for pooled data, p less than 0.001). The results suggest that impedance cardiograms provide reliable estimates of changes of beat-by-beat left ventricular stroke volumes and reasonable estimates of absolute levels of beat-by-beat stroke volumes in humans.

Low-dose transdermal scopolamine decreases blood pressure in mild essential hypertension.

BACKGROUND: Increasing cardiovascular parasympathetic nervous activity could have antihypertensive effects. Low-dose transdermal scopolamine increases vagal-cardiac modulation of sinus node and baroreflex sensitivity in healthy subjects and in cardiac patients. OBJECTIVE: To study the short-term effects of transdermal scopolamine on blood pressure and cardiovascular autonomic control in patients with mild essential hypertension. DESIGN: A randomized, double-blind, placebo-controlled crossover trial with 12 untreated middle-aged [aged 39+/-5 years (mean+/-SD)] patients with mild essential hypertension. METHODS: We recorded the electrocardiogram, auscultatory sphygmomanometric and continuous photoplethysmographic finger arterial pressure, and spirometry signals with patients supine and 70 degrees tilted during controlled (0.25 Hz) breathing. Cardiovascular autonomic regulation was analyzed with power spectrum analysis of R-R interval and arterial pressure variability and a spontaneous sequence method for baroreflex sensitivity. In addition, a deep-breathing test was performed to assess maximal breathing-related sinus arrhythmia. RESULTS: Transdermal scopolamine treatment significantly decreased blood pressure both when patients lay supine and when they were in the 70 degrees tilted position. Scopolamine also slowed heart rate and increased baroreflex sensitivity and R-R interval high-frequency variability for both body positionings. In addition, scopolamine accentuated respiratory sinus arrhythmia during deep breathing and blunted the tilt-induced increase in heart rate. Scopolamine did not affect blood pressure variability. CONCLUSIONS: Transdermal scopolamine decreases arterial pressure, increases baroreflex sensitivity and accentuates vagal-cardiac modulation of sinus node in patients with mild hypertension. Our study supports the hypothesis that increasing cardiovascular parasympathetic activity could have antihypertensive effects in essential hypertension.

Increased vagal cardiac nerve traffic prolongs ventricular refractoriness in patients undergoing electrophysiology testing.

Stimulation of the vagus nerve in animals causes prolongation of sinus cycle length, atrioventricular nodal conduction and ventricular refractoriness. Vagal stimulation appears to have a protective effect in animal models of sudden death. The electrophysiologic effects of enhanced vagal activity on right ventricular (RV) refractoriness in man have not been studied previously. The comparative effects of enhanced vagal tone (neck suction to -60 mm Hg) on sinus cycle length and RV refractoriness were assessed in 26 patients. The electrophysiologic effects of vagal activation by stimulation of carotid baroreceptors with neck suction were compared to the effect of carotid and aortic baroreceptor stimulation with phenylephrine infusion in 12 patients. During neck suction, mean sinus cycle length (819 +/- 32 ms) was prolonged by 146 +/- 20 ms (p less than 0.0001). The mean RV effective refractory period (ERP) and functional refractory period (FRP) were prolonged by 4 +/- 1 ms and 5 +/- 1 ms (p = 0.0001 and 0.0002, respectively). The mean change in RV ERP and FRP correlated with the peak change in sinus cycle length during neck suction (r = 0.46 and r = 0.58, respectively). During intravenous phenylephrine infusion, the mean change in RV ERP and FRP was 5 +/- 2 ms (p less than 0.04) and 10 +/- 3 ms (p less than 0.01), respectively. These results show that reflex vagal stimulation with neck suction or phenylephrine infusion causes a small but significant prolongation in RV refractoriness. These findings imply that the potential benefits of enhanced vagal tone in preventing sudden death may be indirectly mediated by changes in ventricular refractoriness.

Subnormal parasympathetic activity after cardiac transplantation.

Heart period variability (standard deviation of 120 consecutive RR or PP intervals) was used to assess baseline parasympathetic activity in 18 patients with congestive heart failure before and after orthotopic cardiac transplantation, and was compared to that of 16 age-matched control subjects. Mean heart period variability (+/- standard error of the mean) was significantly greater (p less than 0.05) in control subjects (58 +/- 5 ms) than in the patients at any time before or after transplantation. Heart period variability of innervated recipient atria did not change significantly early (1 to 4 weeks) after transplantation (16 +/- 2 to 24 +/- 5 ms; p = 0.11), but increased significantly between weeks 15 and 37 after transplantation (30 +/- 5 ms, p less than 0.002 versus before transplantation). A stepwise regression model (R2 = 0.35; p = 0.01) showed that heart period variability was directly related to time after transplantation and inversely related to systolic arterial pressure after transplantation and degree of rejection. Heart period variability of the denervated donor atria did not change from early to late periods after transplantation, suggesting that vagal reinnervation of the donor heart had not occurred. These data indicate that baseline parasympathetic activity does not increase significantly during the first month after transplantation but increases significantly between months 3 and 6.

Directionally opposite left atrial and ventricular volume changes during lower body suction.

In animals, sympathetic responses to orthostasis are regulated in part by cardiopulmonary afferents arising from atrial and ventricular baroreceptors. To determine the relative importance of these baroreceptor regions in the cardiopulmonary baroreflex of normal humans, simultaneous measurements of left atrial and right and left ventricular volumes (cine computed tomography), invasive hemodynamics, forearm vascular resistance (plethysmography), and efferent sympathetic nerve activity to muscle (microneurography) were obtained under control conditions and with nonhypotensive lower body negative pressure (-10 mmHg, LBNP-10) in nine normal human subjects. LBNP-10 did not alter heart rate or mean systemic arterial pressure, but it did produce significant decreases in pulmonary artery diastolic and right atrial pressures. This reduction in cardiac filling pressures resulted in efferent sympathoexcitation evidenced by increases in forearm vascular resistance and efferent sympathetic nerve activity to the muscle. LBNP-10 did not alter end-diastolic volume of the left or the right ventricle. Similarly, ventricular stroke volume was unchanged during LBNP-10, as assessed by cine computed tomography or thermodilution techniques. In contrast, LBNP-10 resulted in a significant decrease in left atrial volume. Thus, LBNP produced a significant decrease in cardiac filling pressures and left atrial volumes with resultant reflex sympathoexcitation, whereas ventricular volumes were unchanged. These observations suggest an important role for left atrial (nonventricular) baroreceptor afferents in the cardiopulmonary baroreflex of normal humans.

Isometric exercise modifies autonomic baroreflex responses in humans.

The influence of brief, moderate isometric exercise on the earliest vagal and sympathetic responses to changes of afferent carotid baroreceptor activity was studied in 10 healthy young men and women. Vagal-cardiac nerve activity was estimated from changes of electrocardiographic R-R intervals, and postganglionic peroneal nerve muscle sympathetic activity was measured directly from microneurographic recordings. Carotid baroreceptor activity was altered with 5-s periods of 30 Torr pressure or suction applied to a neck chamber during held expiration. Brief handgrip (30% of maximum) significantly reduced base-line R-R intervals, did not modify reductions of R-R intervals during neck pressure, and significantly reduced increases of R-R intervals during neck suction. Handgrip did not significantly increase base-line sympathetic activity from resting levels, but it significantly diminished increases of sympathetic activity during neck pressure and augmented reductions of sympathetic activity during neck suction. Our results suggest that exercise modifies, in small but significant ways, early sympathetic and vagal responses to abrupt changes of arterial baroreceptor input in humans.

Preservation of oscillations in postocclusive reactive hyperemia.

Oscillations in skin blood flow (SkBF) during postocclusive reactive hyperemia are believed to be due to locally mediated events in the microcirculation. We characterized the activity of these oscillations in nine healthy young men who underwent 0, 10, and 40 Torr of lower body negative pressure (LBNP). Postocclusive SkBF was estimated in both forearms simultaneously in a stable thermal environment with laser-Doppler velocimetry. Periodic behavior of SkBF was characterized by frequency-domain power spectral analysis. LBNP at 40 Torr increased heart rate, decreased forearm blood flow, and decreased postocclusive SkBF amplitude but did not change the periodicity of SkBF in the frequency response range that is characteristic of postischemic SkBF oscillations (0.11 +/- 0.04 Hz). We observed that LBNP did not alter the frequency response of the postocclusive SkBF as quantified in the periodogram, even though the amplitude of the SkBF was markedly diminished as a part of the general decrease in arm blood flow. We found inferential evidence for a disseminated common pacemaker mechanism that performs similarly at distant sites. We conclude that the LBNP baroreflex-mediated modulation of SkBF reduces the amplitude but does not change the frequency behavior of postocclusive SkBF. We propose on the basis of our findings that the preservation of vasomotion suggests that this phenomenon is an adaptation to the ischemic changes induced by disruption of blood flow.

Important influence of respiration on human R-R interval power spectra is largely ignored.

Frequency-domain analyses of R-R intervals are used widely to estimate levels of autonomic neural traffic to the human heart. Because respiration modulates autonomic activity, we determined for nine healthy subjects the influence of breathing frequency and tidal volume on R-R interval power spectra (fast-Fourier transform method). We also surveyed published literature to determine current practices in this burgeoning field of scientific inquiry. Supine subjects breathed at rates of 6, 7.5, 10, 15, 17.1, 20, and 24 breaths/min and with nominal tidal volumes of 1,000 and 1,500 ml. R-R interval power at respiratory and low (0.06-0.14 Hz) frequencies declined significantly as breathing frequency increased. R-R interval power at respiratory frequencies was significantly greater at a tidal volume of 1,500 than 1,000 ml. Neither breathing frequency nor tidal volume influenced average R-R intervals significantly. Our review of studies reporting human R-R interval power spectra showed that 51% of the studies controlled respiratory rate, 11% controlled tidal volume, and 11% controlled both respiratory rate and tidal volume. The major implications of our analyses are that breathing parameters strongly influence low-frequency as well as respiratory frequency R-R interval power spectra and that this influence is largely ignored in published research.

Short-duration spaceflight impairs human carotid baroreceptor-cardiac reflex responses.

Orthostatic intolerance is a predictable but poorly understood consequence of space travel. Because arterial baroreceptors modulate abrupt pressure transients, we tested the hypothesis that spaceflight impairs baroreflex mechanisms. We studied vagally mediated carotid baroreceptor-cardiac reflex responses (provoked by neck pressure changes) in the supine position and heart rate and blood pressure in the supine and standing positions in 16 astronauts before and after 4- to 5-day Space Shuttle missions. On landing day, resting R-R intervals and standard deviations, and the slope, range, and position of operational points on the carotid transmural pressure-sinus node response relation were all reduced relative to preflight. Stand tests on landing day revealed two separate groups (one maintained standing arterial pressure better) that were separated by preflight slopes, operational points, and supine and standing R-R intervals and by preflight-to-postflight changes in standing pressures, body weights, and operational points. Our results suggest that short-duration spaceflight leads to significant reductions in vagal control of the sinus node that may contribute to, but do not account completely for, orthostatic intolerance.