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R F Rea

Publications and source records attributed to R F Rea.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of fludrocortisone on sympathetic nerve activity in humans.

Fludrocortisone reduces plasma norepinephrine in healthy humans, but forearm vascular and pressor responses to norepinephrine are potentiated. The effects of fludrocortisone on sympathetic nerve activity in healthy humans are not known. To investigate these effects we evaluated muscle sympathetic nerve activity, heart rate, and arterial pressure in 11 healthy volunteers during three protocols: (1) before and on day 7 of fludrocortisone (0.4 mg/d) treatment with ad libitum diet (n = 6); (2) before and on day 7 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n = 7); and (3) before and on day 2 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n = 4). Placebo did not alter any parameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Neural control mechanisms and vasovagal syncope.

Patients with recurrent unexplained syncope may have cardioinhibitory and vasodepressor responses provokable with head-up tilt with or without exogenous beta-adrenergic stimulation. Although these responses are believed to be neurally mediated, the neural mechanisms involved are poorly understood. Numerous studies have documented peripheral vasodilation, hypotension, and bradycardia at the time of syncope and several case reports have shown sudden withdrawal of vasoconstrictor sympathetic neural outflow to skeletal muscle in human subjects. In cats and rats, a similar response can be provoked with hemorrhage and is prevented by interruption of cardiac vagal C-fiber afferents. In dogs, however, section of these fibers does not prevent the development of a vasodepressor response. The provocation of vasodepressor syncope during nitroprusside infusion in a heart transplant recipient with presumed ventricular denervation also suggests that cardiac afferent nerves may not be required for the development of vasodepressor responses in humans. Other potential mechanisms include release of endogenous opioids or nitric oxide that may inhibit sympathetic nerve firing, and primary central nervous system activation (as in partial seizures) that triggers cardioinhibitory and vasodepressor responses. This article reviews our current understanding of the mechanisms involved in the development of neurally mediated syncope.

Animals↗
PubMed1993

Muscle sympathetic nerve responses to dynamic one-legged exercise: effect of body posture.

Previous studies examining muscle sympathetic nerve activity (MSNA) during dynamic exercise have focused on upper extremity exercise. The present study was undertaken to investigate 1) MSNA responses to dynamic one-legged knee extensions (DLE) and 2) the role of the cardiopulmonary baroreflexes in the modulation of MSNA responses to DLE. MSNA was measured during 4 min of DLE at 20 (n = 10) and 30 W (n = 9) and during 3 min of DLE at 40 W (n = 9). DLE was performed in the upright (sitting) position and MSNA was recorded in the contralateral leg (peroneal nerve). DLE elicited significant increases in mean arterial pressure (MAP) and heart rate (HR; P < 0.05). In contrast to previous studies using dynamic arm exercise, MSNA (bursts/min) decreased by 25% (P < 0.05) during the first minute of DLE from resting control and remained suppressed during the remaining 3 min of DLE at 20 and 30 W. During the first minute of DLE at 40 W, MSNA (bursts/min) decreased by 18% (P < 0.05), but returned to control levels during the last minute of exercise. Because dynamic leg exercise in the upright position increases venous return, we postulated that upright DLE might increase cardiac filling pressures and stimulate the cardiopulmonary baroreceptors resulting in suppression of MSNA. To investigate this possibility, we measured MSNA and central venous pressure (CVP) during 4 min of both supine and upright DLE at 30 W. MAP, HR, and CVP increased and MSNA decreased from 30 +/- 3 to 22 +/- 3 bursts/min (mean exercise value; P < 0.05) during upright DLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Alterations in reflex function contributing to syncope: orthostatic hypotension, carotid sinus hypersensitivity and drug-induced dysfunction.

Orthostatic hypotension and related neurologic symptoms are frequently encountered in clinical practice. The maintenance of appropriate blood pressure and heart rate responses upon assuming the upright posture are dependent upon: 1. intact mechanical (venous valves) mechanisms, 2. functioning arterial and cardiopulmonary baroreceptors, 3. normal peripheral neural pathways, 4. normal central neural integration, and 5. appropriate neurohormonal secretion. Dysfunction at one or more of these loci may facilitate the occurrence of orthostatic hypotension and syncope. In general, the mechanisms of orthostatic hypotension may be divided into three categories. In the first category, processes interfere with normal compensatory responses to upright posture. Examples of this mechanism include age related autonomic changes, diabetic neuropathy and central nervous system disease such as Shy-Drager syndrome. The second principal mechanism involves overwhelming otherwise normal reflexes by an intense orthostatic stimulus. An obvious example of this mechanism is syncope related to hemorrhage. A final category of orthostatic hypotension relates to interference with reflex responses by drugs that may limit vasoconstriction, heart rate or cardiac output adjustments or exaggerate venous pooling. These are commonly used medications such as vasodilators, beta-adrenergic blockers and nitrates. The treatment of orthostatic hypotension revolves around the recognition of underlying causes or contributing factors amenable to correction or avoidance. Other helpful treatment options include nocturnal head-up tilting and mineralocorticoids, both of which help to expand blood volume. Many other therapeutic agents have been tried in small and selected patient populations, often with disappointing results. While many of the drugs available (phenylephrine, ephedrine, tyramine, dihydroergotamine) can improve upright blood pressure, side effects are common, and supine hypertension is problematic in many patients. Interventions of this type should be carefully initiated in a monitored setting. The carotid sinus is an important component of a neural control system responsible for heart rate and blood pressure homeostasis. Excessive heart rate and blood pressure responses to distortion of the carotid sinus are the basis for the carotid sinus syndrome (CSS). Patients with CSS tend to be elderly males and local pathology in the neck is frequently involved. Atherosclerotic coronary artery disease and hypertension are important clinical correlates. Two major categories of carotid sinus hypersensitivity (CSH) are recognized: cardioinhibitory and vasodepressor. Cardioinhibitory CSH is the most common, and in its purest form consists of sinus bradycardia or arrest, asystole or AV block during carotid sinus massage. This vagally-mediated response is eliminated by atropine. Cardiac pacing is nearly universally successful in preventing severe symptoms.(ABSTRACT TRUNCATED AT 400 WORDS)

Arrhythmias, Cardiac↗
PubMed1992

Effects of quinidine on vascular resistance and sympathetic nerve activity in humans.

OBJECTIVES: The purpose of the present study was to test the hypothesis that intravenous quinidine, unlike procainamide, causes direct vasodilation and reflexly mediated increases in sympathetic nerve activity. BACKGROUND: Intravenous quinidine can cause significant hypotension. Animal experiments have suggested that quinidine blocks alpha-receptors and also relaxes vascular smooth muscle by a nonadrenergic mechanism. In a recent study we showed that intravenous procainamide causes peripheral vasodilation, hypotension and inhibition of sympathetic nerve activity in humans. Intraarterial procainamide, however, did not cause vasodilation. METHODS: Postganglionic muscle sympathetic nerve traffic was recorded from the peroneal nerve at the fibular head with tungsten microelectrodes, and forearm blood flow was measured with venous occlusion plethysmography. Central venous pressure was measured directly. The direct effects of quinidine on vascular resistance were determined with brachial artery quinidine infusions and measurement of ipsilateral forearm blood flow. RESULTS: In eight normal subjects intravenous quinidine (8 mg/kg body weight infused for 27 min) decreased mean arterial pressure from 87 +/- 3 (mean +/- SE) to 83 +/- 3 mm Hg, central venous pressure from 6.3 +/- 0.6 to 5.0 +/- 0.7 mm Hg and forearm vascular resistance from 32.2 +/- 5.5 to 25.3 +/- 4.7 U (all p < 0.05). Heart rate increased from 67 +/- 4 to 77 +/- 5 beats/min and muscle sympathetic nerve activity from 288 +/- 70 to 660 +/- 151 U/min (both p < 0.05). In five subjects intravenous nitroprusside that caused similar hemodynamic effects produced similar increases in sympathetic nerve activity. In eight subjects graded infusions of quinidine into the brachial artery (0.37, 0.74 and 1.48 mg/min) produced dose-dependent decreases in ipsilateral forearm vascular resistance and marked attenuation of forearm vasoconstriction caused by the cold pressor test. CONCLUSIONS: These data show that quinidine, unlike procainamide, causes vasodilation directly and, when given intravenously, is associated with baroreflex-mediated increases in sympathetic nerve activity.

Adult↗
PubMed1992

A signal-averaging technique for the analysis of human muscle sympathetic nerve activity.

We present a signal-averaging technique for analysis of human muscle sympathetic nerve activity (SNA). Nerve traffic was averaged by coupling signal acquisition to electrocardiographic R waves. The amplitude of the averaged waveform was multiplied by the number of R waves sampled to provide a measure of SNA in arbitrary units. This was compared with SNA measured by manual digitization of hard-copy records. In nine volunteers, SNA was increased or decreased with stepwise infusions of nitroprusside or phenylephrine: there were 10 5-min periods of data in each subject. Across all subjects, the correlation between manual and signal-averaged measures of SNA was excellent during both nitroprusside (r = 0.98) and phenylephrine infusions (r = 0.91) and the slopes of the regression lines were near unity. In three periods of data collection, electrical artifacts were added randomly at frequencies of 0.5 and 0.07 Hz during playback of the signal into the computer. Signal-averaged estimates of SNA were unaffected by artifacts. This technique provides reliable observer-independent measures of SNA.

Blood Pressure↗
PubMed1992

Muscle sympathetic nerve responses to static leg exercise.

Previous studies of muscle sympathetic nerve activity (MSNA) during static exercise have employed predominantly the arms. These studies have revealed striking increases in arm and leg MSNA during static handgrip (SHG) and postexercise circulatory arrest (PECA). The purpose of this study was to examine MSNA during static leg exercise (SLE) at intensities and duration commonly used during SHG followed by PECA. During 2 min of SLE (static knee extension) at 10% of maximal voluntary contraction (MVC; n = 18) in the sitting position, mean arterial pressure and heart rate increased significantly. Surprisingly, MSNA in the contralateral leg did not increase above control levels during SLE but rather decreased (23 +/- 5%; P < 0.05) during the 1st min of SLE at 10% MVC. We compared MSNA responses to SHG and SLE (n = 8) at 30% MVC. SHG and SLE elicited comparable increases (P < 0.05) in arterial pressure and heart rate, but SHG elicited significant increases in MSNA, whereas SLE did not. During PECA after SHG and SLE, mean arterial pressure remained significantly above control. However, MSNA was unchanged during PECA after SLE but was significantly greater than control during PECA after SHG. Because previous studies have indicated differences in MSNA responses to the arm and leg, we measured arm and leg MSNA simultaneously in six subjects during SLE at 20% MVC and PECA. During SLE and PECA, MSNA in the contralateral arm and leg did not differ significantly from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗
PubMed1992

Hydrogen ion concentration is not the sole determinant of muscle metaboreceptor responses in humans.

We examined the effects of exercise conditioning on muscle sympathetic nerve activity (MSNA) during handgrip and posthandgrip circulatory arrest (PHG-CA). Two conditioning stimuli were studied: forearm dominance and bodybuilding. Static handgrip at 30% maximal voluntary contraction followed by PHG-CA led to a rise in MSNA smaller in dominant than in nondominant forearms (99% vs. 222%; P less than 0.02) and in body builders than in normal volunteers (28% vs. 244%; P less than 0.01). Separate 31P NMR experiments showed no effect of dominance on forearm pH but a pH in bodybuilders higher (6.88) than in normal volunteers (6.79; P less than 0.02) during PHG-CA. Our second goal was to determine if factors besides attenuated [H+] contribute to this conditioning effect. If differences in MSNA during exercise were noted at the same pH, then other mechanisms must contribute to the training effect. We measured MSNA during ischemic fatiguing handgrip. No dominance or bodybuilding effect on pH was noted. However, we noted increases in MSNA smaller in dominant than nondominant forearms (212% vs. 322%; P less than 0.02) and in bodybuilders than in normal volunteers (161% vs. 334%; P less than 0.01). In summary, MSNA responses were less during exercise of conditioned limbs. Factors aside from a lessening of muscle acidosis contribute to this effect.

Adult↗
PubMed1991

Yohimbine increases sympathetic nerve activity and norepinephrine spillover in normal volunteers.

It has been difficult to examine clinically the physiological role of central and peripheral alpha 2-adrenoceptors in humans. We simultaneously measured directly recorded peroneal skeletal muscle sympathoneural activity (MSNA) and the rate of appearance (spillover) of norepinephrine (NE) in forearm venous and arterial plasma before and at 15 min during intravenous administration of the alpha 2-blocker yohimbine (Yoh, 125 micrograms/kg bolus, 1 microgram.kg-1.min-1 infusion) in seven normal volunteers. Yoh administration increased mean arterial pressure by 16% (P less than 0.005), heart rate by 8% (P less than 0.05), and forearm vascular resistance by 67% (P less than 0.05). MSNA was increased by 73% (P less than 0.05), NE spillover into arterial blood by 125% (P less than 0.05), and forearm NE spillover (FSO) by 337% (P less than 0.005). Ganglion blockade by trimethaphan during Yoh infusion decreased MSNA to below detection limits and reversed Yoh-induced increases in arterial concentrations of NE and epinephrine. The results demonstrate that Yoh administration increases sympathoadrenal outflow. Because the mean increase of FSO was much larger than that of MSNA, the results suggest that alpha 2-adrenoceptors on sympathetic nerve endings modulate the neuronal release of NE for a given amount of sympathetic nerve traffic in humans; this effect seems prominent in the human limb.

Adrenocorticotropic Hormone↗
PubMed1991

Comparison of muscle sympathetic responses to hemorrhage and lower body negative pressure in humans.

We compared changes in muscle sympathetic nerve activity (SNA) during graded lower body negative pressure (LBNP) and 450 ml of hemorrhage in nine healthy volunteers. During LBNP, central venous pressure (CVP) decreased from 6.1 +/- 0.4 to 4.5 +/- 0.5 (LBNP -5 mmHg), 3.4 +/- 0.6 (LBNP -10 mmHg), and 2.3 +/- 0.6 mmHg (LBNP -15 mmHg), and there were progressive increases in SNA at each level of LBNP. The slope relating percent change in SNA to change in CVP during LBNP (mean +/- SE) was 27 +/- 11%/mmHg. Hemorrhage of 450 ml at a mean rate of 71 +/- 5 ml/min decreased CVP from 6.1 +/- 0.5 to 3.7 +/- 0.5 mmHg and increased SNA by 47 +/- 11%. The increase in SNA during hemorrhage was not significantly different from the increase in SNA predicted by the slope relating percent change in SNA to change in CVP during LBNP. These data show that nonhypotensive hemorrhage causes sympathoexcitation and that sympathetic responses to LBNP and nonhypotensive hemorrhage are similar in humans.

Adult↗
PubMed1991

Inhibitory effects of procainamide on sympathetic nerve activity in humans.

In experimental animals, procainamide causes hypotension and reductions in efferent vasoconstrictor sympathetic outflow that may result from ganglionic blockade or central nervous system sympathetic inhibition. To test the hypothesis that procainamide decreases sympathetic nerve activity (SNA) in humans, we recorded postganglionic SNA in seven normal subjects in the baseline state and during infusions of procainamide HCl at 50 mg/min (loading) and 8 mg/min (maintenance). At the end of the loading infusion, mean arterial pressure (MAP) had decreased from 88.5 +/- 2.4 (mean +/- SEM) to 81.5 +/- 3.2 mm Hg (p less than 0.05), central venous pressure from 6.7 +/- 0.7 to 5.4 +/- 0.9 mm Hg (p less than 0.05), forearm vascular resistance (FVR) from 28 +/- 4.8 to 22.3 +/- 5.1 resistance units (p less than 0.05), and SNA from 259 +/- 47 to 94 +/- 26 units/min (p less than 0.05). These changes persisted during the maintenance infusion. Increased levels of SNA, FVR, and MAP provoked by the cold pressor test were reduced significantly by intravenous procainamide. In eight other subjects, intravenous procainamide HCl (15 mg/kg at 50 mg/min) caused dose-dependent inhibition of SNA that reversed as blood concentrations fell during drug washout. To determine if procainamide causes direct vasodilation, in nine subjects, graded infusions were delivered into the brachial artery at doses that produced no systemic effect. Ipsilateral FVR tended to increase during local intra-arterial infusion of procainamide. These data show that intravenous procainamide causes hypotension, vasodilation, and sympathetic withdrawal. Vasodilation does not result from a direct vasorelaxant effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Heart rate and muscle sympathetic nerve variability during reflex changes of autonomic activity.

Low-frequency (less than 0.15 Hz) fluctuations of heart rate are increased by maneuvers, such as standing or hemorrhage, that increase sympathetic outflow to the heart and vasculature. To test the hypothesis that low-frequency heart rate fluctuations provide an index of sympathetic efferent activity, we compared power spectral measures of heart rate variability with two measures of sympathetic outflow, peroneal nerve sympathetic activity and antecubital vein plasma norepinephrine concentrations. Autonomic outflow was varied with graded stepwise infusions of nitroprusside and phenylephrine, which lowered or raised average diastolic pressures by approximately 15 mmHg. Before vasoactive drug infusions, no spectral measure of heart rate variability correlated significantly with muscle sympathetic activity, plasma norepinephrine concentration, average heart rate, or arterial pressure. During increases of muscle sympathetic activity and probable reductions of cardiac vagal activity induced by nitroprusside, the fraction of heart rate spectral power at low frequencies, but not the absolute value, correlated significantly with muscle sympathetic activity and plasma norepinephrine. However, during reductions of muscle sympathetic activity and probable elevations of cardiac vagal activity induced by phenylephrine, no measure of heart rate variability correlated significantly with muscle sympathetic activity. These findings can be explained by a model of heart rate control in which low-frequency heart rate fluctuations result from changing levels of both the sympathetic and parasympathetic inputs to the sinoatrial node.

Adult↗
PubMed1990

Relation of plasma norepinephrine and sympathetic traffic during hypotension in humans.

We compared changes in antecubital venous plasma levels of norepinephrine (NE) and peroneal nerve muscle sympathetic activity (MSA) during and after nitroprusside (NP)-induced hypotension in nine healthy volunteers. During NP, MSA increased at 98.7%/min, peaked at 4 min at 399 +/- 77% (SE) of base line, and then decreased, so that at the end of the infusion MSA was 298 +/- 39% of base line. NE increased at 9.2%/min and peaked at 14.5 min at 231 +/- 31% of base line just before the end of the infusion. Percent increases of MSA and NE near the end of NP were not significantly different. The time-to-peak NE lagged the time-to-peak MSA by nearly 10 min. These results suggest that during increases of sympathetic outflow diffusion and washout of NE from neuroeffector junctions result in delayed increases in NE in the venous drainage; percent changes in MSA and NE during prolonged stable mild hypotension are similar. The findings provide conditional support for the use of changes in NE to indicate changes in sympathetic traffic.

Adult↗
PubMed1990

Baroreflex control of muscle sympathetic nerve activity in borderline hypertension.

Patients with borderline hypertension have exaggerated vascular responses to orthostatic stress produced by tilt or lower body negative pressure (LBNP). It has been suggested that 1) in the supine position, these patients have augmented activity of cardiopulmonary baroreceptors that exerts an increased restraint on sympathetic vasoconstrictor tone; 2) withdrawal of this augmented inhibitory baroreceptor activity during orthostatic stress elicits augmented reflex sympathetic vasoconstrictor outflow; and 3) augmented cardiopulmonary baroreceptor activity may be secondary to impaired arterial baroreflex mechanisms. To test these hypotheses, we recorded muscle sympathetic nerve activity from the peroneal nerve in seven borderline hypertensive subjects and seven age-, sex-, and weight-matched normotensive subjects during three levels of nonhypotensive LBNP and infusions of phenylephrine and nitroprusside. During LBNP, reductions of central venous pressure were similar in borderline hypertensive and normotensive subjects, and arterial pressure and heart rate values were unchanged. Increases of sympathetic nerve activity, however, were significantly greater in borderline hypertensive than in normotensive subjects at each level of LBNP, indicating an augmented gain of the cardiopulmonary baroreflex. To determine whether this augmentation is related to impairment of arterial baroreflexes, we measured changes of sympathetic nerve activity during increases and decreases of arterial pressure produced with infusions of intravenous phenylephrine and nitroprusside. Central venous pressure was held at control levels by LBNP during phenylephrine and saline infusion during nitroprusside. Changes of sympathetic nerve activity during alterations of arterial pressure were similar in borderline hypertensive and normotensive subjects. These data show that cardiopulmonary baroreflex control of SNA is augmented in borderline hypertensive subjects and that this augmentation does not result from an attenuation of the arterial baroreflex.

Blood Pressure↗
PubMed1990

Reflex control of sympathetic nerve activity in dopamine beta-hydroxylase deficiency.

Patients with autonomic failure secondary to dopamine beta-hydroxylase deficiency lack the enzyme activity necessary for the conversion of dopamine to norepinephrine in sympathetic nerve terminals and the adrenal medulla. These patients have virtually undetectable norepinephrine and epinephrine in plasma and cerebrospinal fluid. The presence of intact sympathetic nerve activity in these patients has been suggested by the enhanced release of dopamine (but not norepinephrine) in response to maneuvers that augment sympathetic outflow in normal subjects. In the present study, we recorded sympathetic nerve traffic by using microneurography in a patient with dopamine beta-hydroxylase deficiency and measured sympathetic neural responses to static exercise, the cold pressor test, and pharmacological alterations of blood pressure. At rest, sympathetic nerve activity was abundant and was modulated in a normal manner by handgrip (+278%), the cold pressor test (+169%), hypotension induced with isoproterenol (+102%), and hypertension induced with phenylephrine (-85%). These results provide the first electrophysiological evidence for intact regulation of sympathetic neural outflow in a patient with dopamine beta-hydroxylase deficiency and suggest that central norepinephrine and epinephrine pathways believed essential for the control of sympathetic neurotransmission in humans may be supplanted by alternative redundant mechanisms.

Adult↗
PubMed1990

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.

Adult↗