Biomedical subjects

J S Floras

Publications and source records attributed to J S Floras.

At least 19 recordsLinked to original sources

PubMed2005

Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) elicits a number of cardiovascular perturbations that could lead acutely or chronically to increased ventricular ectopy in patients with heart failure (HF). We tested the hypothesis that treatment of OSA with continuous positive airway pressure (CPAP) in patients with HF would reduce the frequency of ventricular premature beats (VPBs) during sleep in association with reduced sympathetic nervous system activity. METHODS: Following optimisation of medical treatment, 18 HF patients with OSA and >10 VPBs per hour of sleep were randomised to a control group (n = 8) or a treatment group who received CPAP (n = 10). The frequency of VPBs and urinary norepinephrine (noradrenaline) concentrations during total sleep time were determined at baseline and after 1 month. RESULTS: Control patients did not experience any significant changes in apnoea-hypopnoea index (AHI), mean nocturnal O(2) saturation, or the frequency of VPBs. In contrast, there was a significant reduction in AHI (p<0.001), an increase in minimum O(2) saturation (p = 0.05), a reduction in urinary norepinephrine concentrations (p = 0.009), and a 58% reduction in the frequency of VPBs during total sleep (from mean (SE) 170 (65) to 70 (28) per hour, p = 0.011) after 1 month of CPAP treatment. CONCLUSIONS: In patients with HF, treatment of co-existing OSA by CPAP reduces the frequency of VPBs during sleep. These data suggest that reductions in VPBs and other ventricular arrhythmias through treatment of OSA might improve the prognosis in patients with HF.

Arrhythmias, Cardiac↗

PubMed2004

Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations.

Our objective was to compare brachial artery endothelium dependent and independent vasodilation in lupus patients and healthy females, by means of high-resolution noninvasive brachial artery ultrasound. Endothelially mediated vasodilation was estimated noninvasively by examination of brachial artery responses to postischemic reactive hyperemia and endothelial independent vasodilation from response to sublingual glycerlynitrate (GTN) using high-resolution external vascular ultrasound. Five patients with known coronary artery disease (CAD), five with subclinical CAD, five with no CAD and five control subjects were assessed. Endothelium dependent vasodilation was significantly blunted in lupus patients with CAD as compared with healthy female controls (0.11 versus 11.1%, P = 0.018). Corresponding values for lupus patients with subclinical CAD and no CAD were 11 and 9.6%, respectively. For each subject, endothelium dependent vasodilation (EDV) was related to endothelium independent vasodilation (EIV) to adjust for varying vascular smooth muscle responses to GTN in individual subjects. This ratio was markedly depressed in lupus patients with CAD as compared with control subjects (0.12 versus 1.15). The corresponding EDV/EIV ratios for patients with subclinical CAD and no CAD were similar at 0.69 and 0.65, respectively. The conclusion was that flow mediated vasodilation in lupus patients with coronary artery disease is markedly depressed as compared to healthy subjects.

Adult↗

PubMed2003

Sympathetic activation in human heart failure: diverse mechanisms, therapeutic opportunities.

Plasma noradrenaline (NA) concentrations relate both to the severity of heart failure, and to its impact on survival, but have shortcomings that limit their usefulness as measures of sympathetic discharge. Neural recordings and the isotopic dilution method for determining organ-specific rates of NA spillover into plasma have enhanced our understanding of mechanisms responsible for sympathetic activation. Because the arterial baroreceptor reflex control of heart rate is impaired in heart failure, a parallel reduction in the reflex inhibition of sympathetic outflow has been assumed. However, human heart failure is characterized by rapidly responsive arterial baroreflex regulation of muscle sympathetic nerve activity (MSNA), attenuated cardiopulmonary reflex modulation of MSNA, and activation of a cardiac-specific sympatho-excitatory reflex related to increased cardiopulmonary filling pressures. Together, these baroreceptor mediated mechanisms account only, in part, for the time course and magnitude of adrenergic activation in heart failure. Non-baroreflex sympatho-excitatory mechanisms include: a metaboreflex arising from exercising skeletal muscle, mediated, in part, by adenosine, co-existing sleep apnoea, and pre-junctional facilitation of NA release. Thus, sympathetic activation in the setting of impaired systolic function reflects the net balance and interaction between augmented excitatory and diminished inhibitory influences. Variation, between patients, in the dynamics, magnitude and progression of sympathetic activation mandates an individualized approach to investigation and therapy. Excessive sympathetic outflow to the heart and periphery can be addressed by several complimentary strategies: attenuating these sympatho-excitatory stimuli, modulating the neural regulation of NA release, and blocking the actions of catecholamines at post-junctional receptors.

Adenosine↗

PubMed2003

Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex.

This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night's application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3 +/- 6.8 to 126.0 +/- 6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7 +/- 4.5 to 72.9 +/- 4.5). CPAP usage for 2 months was accompanied by an 11.0 +/- 4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4 +/- 4.4 and 9.3 +/- 3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8 +/- 3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.

Adult↗

PubMed2002

Peak oxygen uptake is not determined by cardiac noradrenaline spillover in heart failure.

AIMS: We recently found that resting muscle sympathetic nerve activity is inversely related to peak oxygen uptake (VO(2) peak) in patients with heart failure, suggesting a peripheral neurogenic limit to exercise in heart failure. No such relationship was observed in healthy controls. To determine whether this observation is specific to sympathetic discharge to skeletal muscle, we tested the null hypothesis that VO(2) peak would not relate to resting cardiac noradrenaline spillover, which is also elevated in heart failure. METHODS AND RESULTS: We measured cardiac noradrenaline spillover at rest by a radiotracer technique and VO(2) peak, during cycle ergometry, by open circuit spirometry in 49 heart failure patients (mean age 54.4+/-1.4 (SE)). There was a significant relationship between age and peak VO(2) (P=0.022). There was no significant relationship between cardiac noradrenaline spillover and either absolute or relative VO(2) peak (P=0.136), with age included in a multiple linear regression model, and none between cardiac noradrenaline spillover and the percent predicted VO2) peak achieved (P=0.34). CONCLUSIONS: Reduced exercise capacity in heart failure relates more closely to sympathetic traffic to skeletal muscle than to cardiac sympathetic outflow, as assessed by noradrenaline spillover. This finding lends further support to the concept of a predominantly peripheral neurogenic limit to exercise.

Adrenergic alpha-Agonists↗

PubMed2001

Lack of evidence for peripheral alpha(1)- adrenoceptor blockade during long-term treatment of heart failure with carvedilol.

OBJECTIVES: The purpose of this study was to determine whether carvedilol's alpha(1)-adrenoceptor antagonism persists during long-term therapy of patients with congestive heart failure (CHF). BACKGROUND: Carvedilol and metoprolol differ in that carvedilol also antagonizes beta(2)- and alpha(1)-adrenoceptors. We hypothesized that in contrast to metoprolol, carvedilol would increase calf vascular conductance (CVC), blunt neurally mediated vasoconstriction and attenuate neuroeffector transfer function gain. METHODS: We randomized 36 patients with CHF (age 55 +/- 1 years, ejection fraction 19 +/- 1%, means +/- SE) to either drug. Blood pressure (BP), heart rate, muscle sympathetic nerve activity (MSNA) and CVC were assessed before and after four months of treatment. The variability of BP and MSNA was determined using fast Fourier transformation. RESULTS: Paired data were obtained in 23 (carvedilol, 13; metoprolol, 10) subjects. Both beta-blockers decreased heart rate, but neither affected mean BP or CVC (carvedilol: 0.016 +/- 0.002 to 0.018 +/- 0.003 U; metoprolol: 0.020 +/- 0.002 to 0.020 +/- 0.004 U). Isometric handgrip exercise (30% of maximum) increased heart rate, mean BP and MSNA. The calf vasoconstrictor response to handgrip exercise was not affected by carvedilol (from 16 +/- 6 resistance U to 25 +/- 10 resistance U, NS). The gain of the transfer of oscillations in MSNA into BP under resting conditions was not attenuated by carvedilol. CONCLUSIONS: Carvedilol did not increase CVC, blunt the calf vasoconstrictor response to handgrip or attenuate the gain of the neuroeffector transfer function, indicating the absence of functionally important peripheral alpha(1)-adrenoceptor antagonism during long-term treatment of CHF.

Adrenergic Fibers↗

PubMed2001

Nonselective versus selective beta-adrenergic receptor blockade in congestive heart failure: differential effects on sympathetic activity.

BACKGROUND: Activation of the sympathetic nervous system has important prognostic implications in chronic heart failure. Nonselective versus selective beta-adrenergic receptor antagonists may have differential effects on norepinephrine release from nerve terminals mediated by prejunctional beta(2)-adrenergic receptors. METHODS AND RESULTS: Thirty-six patients with chronic heart failure were randomized to the nonselective beta-blocker carvedilol or the selective beta-blocker metoprolol (double-blind). Measurements of hemodynamics and cardiac and systemic norepinephrine spillover as well as microneurographic recordings of muscle sympathetic nerve traffic were made before and after 4 months of therapy. In the carvedilol group (n=17), there were significant reductions in both total body (-1.7+/-0.5 nmol/min, P<0.01) and cardiac norepinephrine spillover (-87+/-29 pmol/min, P<0.01). By contrast, in the metoprolol group (n=14), there were no significant changes in total body or cardiac norepinephrine spillover. Responses in the carvedilol group were significantly different from those observed in the metoprolol group (P<0.05). Both agents caused a reduction in heart rate and increases in pulse pressure, although mean arterial pressure did not change. Importantly, microneurographic measures of sympathetic nerve traffic to skeletal muscle did not change in either group. CONCLUSIONS: Therapy with carvedilol caused significant decreases in systemic and cardiac norepinephrine spillover, an indirect measure of norepinephrine release. Such changes were not observed in patients treated with metoprolol. There was no effect of either agent on sympathetic efferent neuronal discharge to skeletal muscle. These findings suggest that carvedilol, a nonselective beta-blocker, caused its sympathoinhibitory effect by blocking peripheral, prejunctional beta-adrenergic receptors.

Adolescent↗

PubMed2001

Limitations of the use of spectral analysis of heart rate variability for the estimation of cardiac sympathetic activity in heart failure.

Spectral analysis of heart rate variability has gained popularity as a simple, non-invasive tool for assessing autonomic function in both normal subjects and in patients in a variety of clinical settings. However, the use of this method as a means of estimating the magnitude of cardiac sympathetic activation in individual patients with heart failure has proved disappointing, with a lack of concordance with more direct measures of sympathetic outflow. This review will describe the rationale involved in using sympathetic indices obtained from spectral analysis of heart rate variability to assess cardiac sympathetic outflow in normal subjects and patients with heart failure. The specific limitations and technological concerns that dictate how it may most effectively be used in this patient population will be discussed.

Animals↗

PubMed2001

N(G)-monomethyl-L-arginine alters insulin-mediated calf blood flow but not glucose disposal in the elderly.

It has been proposed that an important component of glucose disposal is insulin-mediated vasodilation via a nitric oxide (NO)-dependent mechanism. Normal aging is characterized by a resistance to insulin-mediated glucose disposal and deficient endothelial NO production. Impairment of insulin-mediated vasodilation could contribute to this insulin resistance. We tested the hypothesis that the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) would decrease insulin-mediated calf vasodilation and whole-body glucose disposal in young subjects but would have little or no effect in the elderly. Experiments were performed on healthy young (n = 10) and old (n = 10) subjects on 2 study days. Insulin was infused for 4 hours at 40 mU/m(2)/min (young) and 34 mU/m(2)/min (old) during both studies, and L-NMMA (0.1 mg/kg/min) was coinfused during the last 2 hours of insulin on one of these sessions. Calf blood flow was measured by venous occlusion plethysmography, and calf vascular conductance was derived from calf blood flow and mean arterial blood pressure (MABP). L-NMMA increased whole-body insulin-mediated glucose uptake (IMGU) in young subjects (from 11.22 +/- 0.08 to 12.22 +/- 0.87 mg/kg/min, P <.05) but decreased calf blood flow (from 6.53 +/- 0.62 to 5.49 +/- 0.43 mL/100 mL/min, P <.05). In contrast, L-NMMA had no effect on IMGU in elderly subjects (control v L-NMMA, 7.58 +/- 0.46 v 7.86 +/- 0.37 mg/kg/min, P = nonsignificant) but increased calf blood flow (from 3.65 +/- 0.36 to 4.50 +/- 0.32 mL/100 mL/min, P <.01). L-NMMA decreased calf vascular conductance in young subjects (from 0.083 +/- 0.008 to 0.064 +/- 0.005 mL/100 mL/min/mm Hg, P <.05) but not in the elderly (control v L-NMMA, 0.038 +/- 0.004 v 0.040 +/- 0.002 mL/100 mL/min/mm Hg), consistent with the concept that skeletal muscle endothelial NO production is reduced with age. We therefore conclude that (1) L-NMMA has different or opposite actions on calf blood flow and IMGU in both age groups, indicating that the effect of insulin on skeletal muscle blood flow is independent of its influence on glucose disposal in young and old, and (2) skeletal muscle NO production decreases with age.

Adult↗

PubMed2001

Contrasting effects of L-arginine on insulin-mediated blood flow and glucose disposal in the elderly.

Insulin increases skeletal muscle blood flow in healthy young subjects by a nitric oxide (NO)-dependent mechanism. Impairment of this mechanism may contribute to the insulin resistance of normal aging. We tested the hypothesis that L-arginine, the endogenous precursor for NO synthesis, would augment insulin-mediated vasodilation and in so doing increase insulin-mediated glucose uptake (IMGU) in healthy elderly subjects. Experiments were conducted on healthy young (n = 9; age, 24 +/- 1 years; body mass index, 24 +/- 1 kg/m2) and old (n = 9; age, 77 +/- 2 years; BMI, 25 +/- 1 kg/m2) subjects. Each underwent two euglycemic clamp studies. On both occasions, insulin was infused from 0 to 120 minutes (young, 40 mU/m2/min; old, 34 mU/m2/min). On 1 day, insulin was continued and L-arginine (7.5 mg/kg/min) was coinfused from 120 to 240 minutes. On the second study day, the insulin infusion from 120 minutes onward was adjusted in each subject to match corresponding plasma concentrations during the L-arginine infusion. Calf blood flow was measured bilaterally using venous occlusion plethysmography. Mean arterial blood pressure decreased in response to L-arginine in both young (77 +/- 1 v 73 +/- 1 mm Hg; P < .05) and old (103 +/- 2 v 94 +/- 2 mm Hg; P < .01). Calf vascular conductance increased in young (from 0.094 +/- 0.009 to 0.113 +/- 0.012 mL/100 mL/min/mm Hg; P < .01) and old (from 0.035 +/- 0.003 to 0.050 +/- 0.003 mL/100 mL/min/mm Hg; P < .01), consistent with the concept that the addition of substrate can augment skeletal muscle endothelial NO production in both age groups. Calf blood flow increased in both young (control, 7.04 +/- 0.73; L-arginine, 8.02 +/- 0.78 mL/100 mL/min; P < .05) and old (control, 3.60 +/- 0.27: L-arginine, 4.65 +/- 0.23 mL/100 mL/min; P < .0001) subjects, yet L-arginine had no impact on glucose disposal in either age group. In conclusion, L-arginine caused skeletal muscle vasodilation in the elderly, indicating that this endothelially mediated response is not attenuated with age. However, this increase in blood flow had no impact on insulin-mediated glucose uptake.

Adult↗

PubMed2001

Atrial natriuretic peptide augments the variability of sympathetic nerve activity in human heart failure.

OBJECTIVES: Activation of the sympathetic nervous system, decreased heart rate variability (HRV), and loss of modulation of muscle sympathetic nerve activity (MSNA) within the low frequency (LF, 0.05-0.15 Hz) range are three adverse features of advanced congestive heart failure (CHF). In healthy men, atrial natriuretic peptide (ANP) infusion attenuates reflex increases in MSNA and reduces LF components of HRV spectral power. Sympathoinhibitory actions have also been documented in CHF, but effects on the variability of MSNA and HRV have not been described. DESIGN AND METHODS: Heart rate and MSNA were recorded in 10 men (aged 39 +/- 3 years, mean +/- SE) with dilated cardiomyopathy (mean EF 20 +/- 4%) treated with angiotensin converting enzyme (ACE) inhibitors. Subjects received i.v. ANP (50 microg bolus then 50 ng/kg/min) and nitroglycerin (NTG, 8 mg/min) as a hemodynamic control. Signals at baseline, and 13-20 min into each infusion were submitted to spectral analysis. RESULTS: ANP had no effect on HRV, but increased MSNA LF (from 7.9 +/- 1.5 to 12.1 +/- 2.6 U2; P< 0.02) and total spectral power (from 47.9 +/- 5.4 to 61.9 +/- 6.8 U2; P < 0.05). NTG had no effect on the variability of MSNA or HRV. CONCLUSIONS: In CHF patients receiving ACE inhibitors, ANP (i) does not suppress HRV and (ii) enhances the modulation of MSNA, particularly within the LF range. This latter action is not observed with NTG. These findings suggest beneficial actions of exogenous ANP on neurogenic circulatory control.

Adult↗

PubMed2001

Arterial baroreceptor and cardiopulmonary reflex control of sympathetic outflow in human heart failure.

Several observations indicate that the arterial baroreflex control of sympathetic nerve activity is preserved, even in advanced heart failure. These include: (1) augmentation of muscle sympathetic nerve activity burst amplitude and duration following a premature beat; (2) rapid recognition of changes in blood pressure induced by ventricular arrhythmias; (3) muscle sympathetic alternans and a steep inverse relationship between changes in diastolic pressure and the subsequent sympathetic burst amplitude during pulsus alternans; (4) similar inhibition of muscle sympathetic nerve activity in subjects with normal and impaired left ventricular systolic function by increases in intrathoracic aortic transmural pressure; (5) documentation, by cross-spectral analysis, of similar gain in the transfer function between blood pressure and muscle sympathetic nerve activity in these two groups; and (6) during sodium nitroprusside infusion, similar reflex increases in total body norepinephrine spillover in normal and heart-failure subjects. When nonhypotensive lower-body negative pressure was applied to test the hypothesis that selective reduction of atrial and pulmonary pressures would exert a cardiac sympathoinhibitory response in heart failure, there was no effect in control subjects, but cardiac norepinephrine spillover fell by 25% (P < .05) in those with systolic dysfunction. In summary, human heart failure is characterized by a rapidly responsive and sensitive arterial baroreflex, and by activation of a cardiac sympathoexcitatory reflex related to increased cardiopulmonary filling pressures.

Arteries↗

PubMed2001

Impact of heart failure and exercise capacity on sympathetic response to handgrip exercise.

Peak oxygen uptake (VO(2 peak)) in patients with heart failure (HF) is inversely related to muscle sympathetic nerve activity (MSNA) at rest. We hypothesized that the MSNA response to handgrip exercise is augmented in HF patients and is greatest in those with low VO(2 peak). We studied 14 HF patients and 10 age-matched normal subjects during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%, 30%, and 50% MVC) handgrip exercise that was followed by 2 min of posthandgrip ischemia (PHGI). MSNA was significantly increased during exercise in HF but not normal subjects. Both MSNA and HF levels remained significantly elevated during PHGI after 30% isometric and 50% isotonic handgrip in HF but not normal subjects. HF patients with lower VO(2 peak) (<56% predicted; n = 8) had significantly higher MSNA during rest and exercise than patients with VO(2 peak) > 56% predicted (n = 6) and normal subjects. The muscle metaboreflex contributes to the greater reflex increase in MSNA during ischemic or intense nonischemic exercise in HF. This occurs at a lower threshold than normal and is a function of VO(2 peak).

Blood Pressure↗

PubMed2001

Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure.

Adenosine (Ado) increases muscle sympathetic nerve activity (MSNA) reflexively. Plasma Ado and MSNA are elevated in heart failure (HF). We tested the hypothesis that Ado receptor blockade by caffeine would attenuate reflex MSNA responses to handgrip (HG) and posthandgrip ischemia (PHGI) and that this action would be more prominent in HF subjects than in normal subjects. We studied 12 HF subjects and 10 age-matched normal subjects after either saline or caffeine (4 mg/kg) infusion during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%, 30%, and 50%) HG exercise, followed by 2 min of PHGI. In normal subjects, caffeine did not block increases in MSNA during PHGI after 50% HG. In HF subjects, caffeine abolished MSNA responses to PHGI after both isometric and 50% isotonic exercise (P < 0.05) but MSNA responses during HG were unaffected. These findings are consistent with muscle metaboreflex stimulation by endogenous Ado during ischemic or intense nonischemic HG in HF and suggest an important sympathoexcitatory role for endogenous Ado during exercise in this condition.

Adenosine↗

PubMed2001

Effect of oral contraceptives on the renin angiotensin system and renal function.

We examined the effect of oral contraceptive (OC) usage on the renin angiotensin system (RAS) in two related experiments. In the first experiment, subjects were 34 healthy, normotensive, premenopausal women, 15 OC users and 19 OC nonusers, mean age 25 +/- 1 yr, ingesting a controlled sodium diet. We assessed arterial pressure, glomerular filtration rate, effective renal plasma flow, renal vascular resistance (RVR), and filtration fraction (FF) using inulin and p-aminohippurate clearance techniques, both at baseline and in response to the ANG II receptor blocker losartan. In the second experiment, in similar subjects, 10 OC users and 10 nonusers, we examined circulating RAS components [angiotensinogen, ANG II, aldosterone, plasma renin activity (PRA), and active renin] in response to incremental lower body negative pressure (LBNP), to determine whether renin secretion is suppressed by OC usage. OC users exhibited elevations in systolic blood pressure, RVR, and FF compared with nonusers, which were partially corrected by losartan. In the LBNP phase of the study, baseline measures of PRA, angiotensinogen, ANG II, and aldosterone were all increased in the OC group compared with the control group. Active renin levels did not differ between groups. Incremental LBNP resulted in increased circulating levels of RAS components in both groups. We conclude that the RAS is activated in women using OCs. There was no evidence that decreases in renin secretion result in normalization of the RAS as a whole.

Adult↗

PubMed2001

Differential sympathetic nerve and heart rate spectral effects of nonhypotensive lower body negative pressure.

Lower body negative pressure (LBNP; -5 and -15 mmHg) was applied to 14 men (mean age 44 yr) to test the hypothesis that reductions in preload without effect on stroke volume or blood pressure increase selectively muscle sympathetic nerve activity (MSNA), but not the ratio of low- to high-frequency harmonic component of spectral power (P(L)/P(H)), a coarse-graining power spectral estimate of sympathetic heart rate (HR) modulation. LBNP at -5 mmHg lowered central venous pressure and had no effect on stroke volume (Doppler) or systolic blood pressure but reduced vagal HR modulation. This latter finding, a manifestation of arterial baroreceptor unloading, refutes the concept that low levels of LBNP interrogate, selectively, cardiopulmonary reflexes. MSNA increased, whereas P(L)/P(H) and HR were unchanged. This discordance is consistent with selectivity of efferent sympathetic responses to nonhypotensive LBNP and with unloading of tonically active sympathoexcitatory atrial reflexes in some subjects. Hypotensive LBNP (-15 mmHg) increased MSNA and P(L)/P(H), but there was no correlation between these changes within subjects. Therefore, HR variability has limited utility as an estimate of the magnitude of orthostatic changes in sympathetic discharge to muscle.

Adult↗

PubMed2001

Hemodynamic effects of simulated obstructive apneas in humans with and without heart failure.

STUDY OBJECTIVES: To determine whether generation of negative intrathoracic pressure during apnea would cause more pronounced and sustained reductions in cardiac output in patients with congestive heart failure (CHF) than in healthy subjects. DESIGN: Physiologic intervention study. SETTING: Cardiorespiratory physiology laboratory. PARTICIPANTS: Nine patients with CHF and nine healthy control subjects matched for age and sex. INTERVENTIONS: Patients with CHF and healthy subjects generated - 30 cm H(2)O of intrathoracic pressure during 15-s Mueller maneuvers (MMs) to simulate the acute hemodynamic effects and aftereffects of obstructive apneas. RESULTS: In both groups, MMs caused an immediate rise in left ventricular transmural pressure during systole (LVPtmsys) [p < 0.05], but in CHF patients, this immediate increase was followed by a significant drop in LVPtmsys (p < 0.05), associated with significantly greater reductions in systolic BP and cardiac index than in healthy subjects (- 25 +/- 3 mm Hg vs - 11 +/- 2 mm Hg [p < 0.05] and - 0.53 +/- 0.11 L/min/m(2) vs - 0.15 +/- 0.11 L/min/m(2) [p < 0.05], respectively). Healthy subjects recovered promptly, but in CHF patients, these adverse hemodynamic effects were sustained following release of the MM. CONCLUSIONS: CHF patients experience more pronounced and sustained reductions in BP and cardiac output both during and following the MM than do healthy subjects. These findings suggest the potential for adverse hemodynamic effects and aftereffects of negative intrathoracic pressure generation during obstructive sleep apnea in patients with CHF.

Blood Pressure↗

PubMed2001

Attenuated cardiac baroreflex in men with presyncope evoked by lower body negative pressure.

Mechanisms responsible for presyncope during lower body negative pressure (LBNP) in otherwise healthy subjects are poorly understood. Muscle sympathetic nerve activity (MSNA), blood pressure, heart rate (HR), HR power spectra, central venous pressure (CVP) and stroke volume were determined in 14 healthy men subjected to incremental LBNP. Of these, seven experienced presyncope at LBNP >-15 mmHg. Subjects who tolerated LBNP >-15 mmHg had significantly lower CVP (2.6+/-1.0 versus 7.2+/-1.2 mmHg; means+/-S.E.M., P<0.02), HR (59+/-2 versus 66+/-3 beats/min, P<0.05) and MSNA burst frequency (29.0+/-2.4 versus 39.0+/-3.5 bursts/min, P<0.05) during supine rest. LBNP at -15 mmHg had no effect on blood pressure, but caused similar and significant reductions in stroke volume and cardiac output in both groups. Subjects who tolerated LBNP had significant reflex increases in HR, MSNA burst frequency and burst amplitude with LBNP of -15 mmHg. These responses were absent in those who experienced presyncope. The gain of the cardiac baroreflex regulation of MSNA was markedly attenuated in pre-syncopal subjects (1.2+/-0.6 versus 8.8+/-1.4 bursts/100 heart beats per mmHg; P<0.001). Healthy subjects who experience presyncope in response to LBNP appear more dependent, when supine, upon MSNA to maintain preload, and less able to increase sympathetic vasoconstrictor discharge to skeletal muscle reflexively in response to orthostatic stimuli.

Adult↗