Effects Of Sympathetic Activation Research Articles

Assessing functional sympatholysis during rhythmic handgrip exercise using Doppler ultrasound and near-infrared spectroscopy: sex differences and test-retest reliability.

The effects of sympathetic activity on vasoconstriction are dampened in active skeletal muscle during exercise, a phenomenon termed functional sympatholysis. Limited work has examined the influence of sex on the magnitude of sympatholysis or the test-retest reliability of measurements. In 16 women and 15 men, forearm blood flow (FBF; Doppler ultrasound), muscle oxygenation (near-infrared spectroscopy, NIRS), and beat-to-beat mean arterial pressure (MAP; photoplethysmography) were measured during lower-body negative pressure (LBNP; -20 mmHg) at rest and simultaneously during rhythmic handgrip exercise (30% maximum contraction). Measures were taken twice within the same visit (separated by 15 min) and repeated on a second visit. Forearm vascular conductance (FVC) was calculated as FBF/MAP. The magnitude of sympatholysis was calculated as the difference of LBNP-induced changes between handgrip and rest. LBNP decreased FBF (Δ-45 ± 15%), FVC (Δ-45 ± 16%), and muscle oxygenation (Δ-14 ± 11%); however, these responses were attenuated when LBNP was applied during rhythmic handgrip exercise (Δ-7 ± 9%, Δ-9 ± 10%, and Δ-6 ± 9%, respectively). The magnitude of sympatholysis was not different between men and women (FBF: 40 ± 16% vs. 35 ± 9%, P = 0.37; FVC: 38 ± 16% vs. 35 ± 11%, P = 0.53; muscle oxygenation: 5 ± 9% vs. 11 ± 10%, P = 0.11). Furthermore, sympatholysis measurements demonstrated good to excellent intraday (intraclass-correlation coefficients; ICC ≥ 0.85) and interday (ICC ≥ 0.72) test-retest reliability (all P ≤ 0.01) in both sexes. The coefficients of variation were larger with NIRS (68-91%) than with Doppler ultrasound (16%-22%) assessments of functional sympatholysis. Collectively, these findings demonstrate that assessments of functional sympatholysis are not impacted by biological sex and that Doppler ultrasound-derived measures of sympatholysis have better within-subject reliability than NIRS-derived measures in young healthy adults.

Sympathetic activity is correlated with satellite cell aging and myogenesis via \u03b22-adrenoceptor

Background and objectiveSympathetic activity plays an important role in the proliferation and differentiation of stem cells, and it changes over time, thereby exerting differential effects on various stem cell types. Aging causes sympathetic hyperactivity in aged tissues and blunts sympathetic nerves regulation, and sympathetic abnormalities play a role in aging-related diseases. Currently, the effect of sympathetic activity on skeletal muscle stem cells, namely satellite cells (SCs), is unclear. This study aimed to investigate the effects of skeletal muscle sympathetic activity on SC aging and skeletal muscle repair.Materials and methodsTo evaluate skeletal muscle and fibrotic areas, numbers of SCs and myonuclei per muscle fiber, β2-adrenoceptor (β2-ADR) expression, muscle repair, and sympathetic innervation in skeletal muscle, aged mice, young mice that underwent chemical sympathectomy (CS) were utilized. Mice with a tibialis anterior muscle injury were treated by barium chloride (BaCl2) and clenbuterol (CLB) in vivo. SCs or C2C12 cells were differentiated into myotubes and treated with or without CLB. Immunofluorescence, western blot, sirius red, and hematoxylin–eosin were used to evaluate SCs, myogenic repair and differentiation.ResultsThe number of SCs, sympathetic activity, and reparability of muscle injury in aged mice were significantly decreased, compared with those in young mice. The above characteristics of young mice that underwent CS were similar to those of aged mice. While CLB promoted the repair of muscle injury in aged and CS mice and ameliorated the reduction in the SC number and sympathetic activity, the effects of CLB on the SCs and sympathetic nerves in young mice were not significant. CLB inhibited the myogenic differentiation of C2C12 cells in vitro. We further found that NF-κB and ERK1/2 signaling pathways were activated during myogenic differentiation, and this process could be inhibited by CLB.ConclusionNormal sympathetic activity promoted the stemness of SCs to thereby maintain a steady state. It also could maintain total and self-renewing number of SCs and maintain a quiescent state, which was correlated with skeletal SCs via β2-ADR. Normal sympathetic activity was also beneficial for the myogenic repair of injured skeletal muscle.

Effects of highly selective sympathectomy on neurogenic bowel dysfunction in spinal cord injury rats

Neurogenic bowel dysfunction, including hyperreflexic and areflexic bowel, is a common complication in patients with spinal cord injury (SCI). We hypothesized that removing part of the colonic sympathetic innervation can alleviate the hyperreflexic bowel, and investigated the effect of sympathectomy on the hyperreflexic bowel of SCI rats. The peri-arterial sympathectomy of the inferior mesenteric artery (PSIMA) was performed in T8 SCI rats. The defecation habits of rats, the water content of fresh faeces, the intestinal transmission function, the defecation pressure of the distal colon, and the down-regulation of Alpha-2 adrenergic receptors in colon secondary to PSIMA were evaluated. The incidence of typical hyperreflexic bowel was 95% in SCI rats. Compared to SCI control rats, PSIMA increased the faecal water content of SCI rats by 5–13% (P < 0.05), the emptying rate of the faeces in colon within 24 h by 14–40% (P < 0.05), and the defecation pressure of colon by 10–11 mmHg (P < 0.05). These effects lasted for at least 12 weeks after PSIMA. Immunofluorescence label showed the secondary down-regulation of Alpha-2 adrenergic receptors after PSIMA occurred mainly in rats’ distal colon. PSIMA mainly removes the sympathetic innervation of the distal colon, and can relieve the hyperreflexic bowel in rats with SCI. The possible mechanism is to reduce the inhibitory effect of sympathetic activity, and enhance the regulatory effect of parasympathetic activity on the colon. This procedure could potentially be used for hyperreflexic bowel in patients with SCI.

Lifelong high‐altitude hypoxia induces arterial baroreflex adaptations: new insights and future directions

Lifelong high‐altitude hypoxia induces arterial baroreflex adaptations: new insights and future directions

Dual optical mapping of the innervated mouse heart reveals unique electrophysiological responses during fight-or-flight

Background: The mouse is a mainstay in cardiovascular research, yet the detailed electrophysiological and Ca2+ handling changes in the intact mouse heart in response to physiological sympathetic activity have never been investigated. In larger mammals, sympathetic activation typically results in increased heart rate (HR), accompanied by shortening of action potential duration (APD) to accommodate shorter cycle lengths and ensure adequate diastolic filling time. However, data on the effects of sympathetic activation on the rodent APD are somewhat inconsistent, with both shortening and prolongation reported. Here, for the first time, we systematically investigated the integrated effects of adrenergic activation and dynamic changes in HR in the mouse heart.

Effects of Sympathetic Activation on Aortic Stiffness in Young Healthy and Hypertensive Adults

Aortic stiffness is a major link between hypertension and cardiovascular risk. Anatomic features of the artery including the smooth muscle regulate aortic stiffness, in part. Importantly, vascular smooth muscle is under sympathetic nervous system control, and thus aortic stiffness may be influenced by the sympathetic nervous system. When exposed to physiological stress, older hypertensive adults demonstrate an exaggerated blood pressure response that may correspond with transient arterial stiffness increases, but this response in young hypertensive adults remains unknown.PURPOSEWe tested the hypothesis that sympathetic activation would increase aortic stiffness in young healthy adults (control, CTL), and that aortic stiffness increases during sympathetic activation would be greater in young hypertensive adults (HTN).METHODSSix healthy controls (males=4, females=2; 28.3±5.5 years; BMI: 23.5 ± 3.5 kg/m2) and three young hypertensive participants (males=2, females=1; 28.3±6.0 years; BMI: 30.3±8.2 kg/m2) were studied. Mean arterial pressure (MAP) and carotid‐femoral pulse wave velocity (PWV) were measured at rest and during 5 min of brachial circulatory occlusion (sympathetic activation condition) that followed isometric handgrip exercise.RESULTSResting MAP was higher in HTN (100±6 mmHg) than CTL (90±5 mmHg; P=.029). Occlusion MAP was also higher in HTN (116±6 mmHg) than CTL (102±7 mmHg; P=.016). Resting PWV was similar between CTL (8.6±1.6 m/s) and HTN (8.1±0.1 m/s; P=.47). The increase in PWV from rest to occlusion (1.2±1.4 m/s) in CTL was not significant (P=.09), whereas the increase in PWV from rest to occlusion (2.0±0.4 m/s) in HTN was significant (P=.01).CONCLUSIONSympathetic activation may significantly increase aortic stiffness in young hypertensive adults, but not young healthy adults.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of pulseless ventricular tachycardia on sympathetic activity

The role of sympathetic activation in the genesis of life threatening ventricular arrhythmia is abundantly documented. The protective effect of sympathetic activation at the time of destabilizing ventricular tachycardia is less well known. Recently, muscle sympathetic nerve activity was recorded at our cardiac electrophysiology laboratory in a 62-year-old man who suffered from severe left ventricular failure. In order to elucidate the complex relationship between arrhythmias and autonomic nervous activity, his muscle sympathetic nerve activity recording depicting response to pulseless ventricular tachycardia is hereby presented.

Patients with solid tumors treated with high-temperature whole body hyperthermia show a redistribution of naive/memory T-cell subtypes

An activation of the immune system might contribute to the therapeutic effect of whole body hyperthermia (WBH) in cancer patients. We explored immune and endocrine responses in patients undergoing high-temperature WBH. Identical parameters were investigated in a separate group of healthy volunteers undergoing physical exercise to rule out effects of sympathetic activation. Lymphocyte subpopulations, lymphocytic expression of a range of adhesion molecules, and serum concentrations of a variety of hormones and cytokines were assessed in cancer patients undergoing high-temperature (60 min at 41.0-41.8 degrees C) WBH (n = 25) and in a separate group of healthy volunteers (n = 10) performing strenuous physical exercise. WBH induced an increase in human growth hormone (hGH), ACTH, and cortisol as well as in TNF-alpha, IL-6, IL-8, and IL-12R. We observed an increase in natural killer (NK) cells and CD56+ NK T cells shortly after initiation of WBH. In contrast, we found a decrease in T cells expressing L-selectin (CD62L) or alpha4beta7 integrin adhesion molecules mediating homing to lymphatic tissues. Accordingly, we observed a decrease in CD45RA+CCR7+ naive and CD45RA-CCR7+ central memory T cells. Numbers of CD45RA-CCR7- memory effector and CD45RA+CCR7 terminally differentiated T cells, on the other hand, remained unchanged. No comparable changes were observed in the group of healthy volunteers. In conclusion, patients with solid tumors treated with WBH show an increase in NK and NK T cells. In a later phase, plasma concentrations of IL-8, hGH, and cortisol increase, correlated with an influx of neutrophils into the peripheral blood. The alterations in T-cell populations suggest that WBH may induce naive and central-memory T cells to enter lymphatic tissue to await antigen exposure and effector T cells to migrate into peripheral tissues to exert their effector function. Although the exercise group may not be an appropriate control to proof the effect of WBH, these changes were not seen in the healthy volunteers performing physical exercise.

Congress of the European Society of Cardiology, 2003.

The voice of Sigmund Freud (1856–1939) was heard at the 2003 Congress of the European Society of Cardiology (ESC), held in his native city of Vienna, Austria. The great biologist and psychologist, had he been alive to attend, would doubtless have paid special attention to presentations on mental disturbance and the heart. An example is depression, an important risk factor for poor outcome after myocardial infarction (MI). At the Congress, a meta-analysis of the published work was reported by Dr J. Van Melle (University Hospital Groningen, Groningen, the Netherlands). His group identified 17 prospective studies of the impact of depression (assessed by established psychiatric methods) on mortality rate and cardiac events in the first 2 years after MI. The 17 studies described results in 3804 patients (12 cohorts), and the combined data pointed to an excess mortality risk of at least twice that of the nondepressed. Odds ratios (with 95% confidence intervals) were 2.58 (1.71 to 3.89) for all-cause mortality, 2.50 (1.71 to 3.68) for cardiac mortality, and 2.75 (1.41 to 5.34) for cardiac events. These results should dispel any residual doubts about the clinical importance of post-MI depression, and other work indicates that physicians can identify the condition with reasonable accuracy simply by asking, “Are you feeling blue or sad? Have you lost interest in your activities?” However, the kind of univariate analyses examined by Dr Van Melle tell us nothing about other relevant factors or even the direction of causation. For example, depression might act indirectly by lessening adherence to drug regimens or by undermining resolve to stop smoking, and an adverse prognostic feature such as left ventricular failure might itself predispose to depression. The matter of cause and effect and the question of whether treatment for depression improves cardiac outcome should both be answerable by prospective trials …

The effect of sympathetic activity on thermal hyperalgesia in capsaicin-treated skin during body cooling and warming

An adrenergic mechanism is thought to contribute to pain in conditions that sometimes develop during chronic inflammation and after nerve or tissue injury. There is some doubt, however, about whether adrenergic activity influences nociception in acute inflammation. To investigate this issue, the noncompetitive alpha-(α) adrenergic antagonist phenoxybenzamine was introduced by iontophoresis into the skin of 16 healthy volunteers either before or after the topical application of capsaicin. When applied before capsaicin, phenoxybenzamine increased thermal hyperalgesia at normal ambient temperatures and during body warming. These findings suggest that phenoxybenzamine blocked an analgesic mechanism when applied before the onset of inflammation. However, this effect disappeared during body cooling. When applied after capsaicin, phenoxybenzamine inhibited thermal hyperalgesia at normal ambient temperatures, and during body warming and cooling. Thus, phenoxybenzamine blocked a hyperalgesic mechanism when applied after the onset of inflammation. It was concluded that the presence of inflammation influences the nociceptive effect of α-adrenergic blockage, possibly by increasing access to excitatory adrenergic receptors on nociceptive afferents. An excitatory adrenergic influence on nociception may overcome an inhibitory adrenergic influence during inflammation.

ANTIHYPERTENSIVE DRUGS AND SYMPATHETIC NERVOUS SYSTEM

Several studies have demonstrated that essential hypertension is accompanied by sympathetic activation, which contributes to blood pressure elevation. Sympathetic activation also has adverse consequences in hypertensive patients beyond initiating blood pressure elevation. There is evidence that neural vasoconstriction has metabolic effects in skeletal muscle, impairing glucose delivery to muscles. In the liver, retarding of post prandial clearance of lipids contributes to hyperlipidemia. Cardiac sympathetic activation is a probable cause of sudden death in hearth failure. A trophic effect of sympathetic activation on cardiovascular growth is also likely, contributing to the development of left ventricular hypertrophy. Consequently, one of the major aims of antihypertensive therapy should be to attenuate sympathetic tone.It is possible that, among the antihypertensive drugs available, those inhibiting the sympathetic nervous system might best reduce cardiovascular risk.

Effects of sympathetic activation and regular periodic breathing on complexity of heart period variability

Background. Heart rate exhibits different levels of complexity which are probably related to the neural autonomic modulation. Aim of the study. The aim is to analyze the effect of the sympathetic activation and of a regular periodical external input on the complexity of heart period. Methods. Fifteen healthy young subjects were recorded at rest during spontaneous breathing, during head-up tilt, and at rest during controlled breathing at different rates (10, 15, and 20 breaths/min). The minimum of corrected conditional entropy (CCE) was used to measure complexity (the higher the minimum, the larger the complexity). Spectral indexes in low and high frequency (LF and HF) bands were calculated as well. Results. CCE minimum was significantly lower during tilt and controlled respiration at 10 breaths/min compared to rest during spontaneous breathing, while LF/HF ratio was larger during tilt but smaller during controlled respiration at 10 breaths/min. During faster respiratory rates CCE minimum and the LF/HF were unchanged. No significant correlation was detected between the CCE minimum and the mean or variance of the heart period. CCE minimum was correlated with LF/HF ratio only at rest and during tilt. Conclusions. These results indicate that complexity of heart period is not related to its mean or variance, does not depend only on regularity of respiration, and is affected by interventions capable of entraining different regulatory mechanisms and reducing the number of temporal scales involved on heart period regulation.

Effect of sympathetic activity on capsaicin-evoked pain, hyperalgesia, and vasodilatation.

Painful nerve and tissue injuries can be exacerbated by activity in sympathetic neurons. The mechanisms of sympathetically maintained pain (SMP) are unclear. To determine the effect of cutaneous sympathetic activity on pain induced by primary afferent C-nociceptor sensitization with capsaicin in humans. In healthy volunteers capsaicin was applied topically (n = 12) or injected into the forearm skin (n = 10) to induce spontaneous pain, dynamic and punctate mechanical hyperalgesia, and antidromic (axon reflex) vasodilatation (flare). Intensity of pain and hyperalgesia, axon reflex vasodilatation (laser Doppler), and flare size and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of high and low sympathetic skin activity induced by whole-body cooling and warming with a thermal suit. By this method sympathetic vasoconstrictor activity is modulated in the widest range that can be achieved physiologically. The degree of vasoconstrictor discharge was monitored by measuring skin blood flow (laser Doppler) and temperature (infrared thermometry) at the index finger. The intensity and spatial distribution of capsaicin-evoked spontaneous pain and dynamic and punctate mechanical hyperalgesia were identical during the presence of high and low sympathetic discharge. Antidromic vasodilatation and flare size were significantly diminished when sympathetic vasoconstrictor neurons were excited. Cutaneous sympathetic vasoconstrictor activity does not influence spontaneous pain and mechanical hyperalgesia after capsaicin-induced C-nociceptor sensitization. When using physiologic stimulation of sympathetic activity, the capsaicin model is not useful for elucidating mechanisms of SMP. In neuropathic pain states with SMP, different mechanisms may be present.

The Sympathetic Nervous System and the Kidney: its Importance in Renal Diseases

There is a two-way relation between the sympathetic nerve system and the kidney. On the one hand the sympathetic nerve system affects renal function, i.e. renal hemodynamics, renin secretion and tubular sodium transport. On the other hand the kidney is the source of activating afferent signals, presumably via stimulation of chemoreceptors and baroreceptors. This concept is supported by clinical observations in endstage and pre-endstage renal disease, where sympathetic overactivity is present. It has been shown to depend on the presence of the diseased kidney and is abolished by bilateral nephrectomy. Experimentally, interruption of afferent nerve traffic by dorsal rhizotomy partially prevents hypertension in renal damage models. Imidazoline-preferring binding sites are found in the kidney. In the rat, natriuresis is elicited by injection of moxonidine into the renal artery. In humans, there is no definite evidence for a natriuretic effect, but some observations point in this direction. In renal disease, the issue arises whether sympathetic overactivity contributes to progression of renal failure. Indirect evidence in this direction could be the marked acceleration of progression by smoking, a state of known sympathetic overactivity. In experimental models of renal damage, treatment with moxonidine in antihypertensive doses markedly attenuated development of glomerulosclerosis. Preliminary observations show that even non-antihypertensive doses of moxonidine interfere with the development of glomerulosclerosis. Sympathicolytic agents are obviously rational in the antihypertensive therapy of the renal patient, because uraemia is a state of sympathetic overactivity and because blood pressure-independent effects of sympathetic activation on progression are likely.

A comparative study of changes operated by sympathetic nervous system activation on spindle afferent discharge and on tonic vibration reflex in rabbit jaw muscles

The effect of sympathetic activation on the spindle afferent response to vibratory stimuli eliciting the tonic vibration reflex in jaw closing muscles was studied in precollicularly decerebrate rabbits. Stimulation of the cervical sympathetic trunk, at frequencies within the physiologic range, consistently induced a decrease in spindle response to muscle vibration, which was often preceded by a transient enhancement. Spindle discharge was usually correlated with the EMG activity in the masseter muscle and the tension reflexly developed by jaw muscles. The changes in spindle response to vibration were superimposed on variations of the basal discharge which exhibited different patterns in the studied units, increases in the firing rate being more frequently observed. These effects were mimicked by close arterial injection of the selective α 1-adrenoceptor agonist phenylephrine. Data presented here suggest that sympathetically-induced modifications of the tonic vibration reflex are due to changes exerted on muscle spindle afferent information.

Differential effects of sympathetic activation on sexual arousal in sexually dysfunctional and functional women.

The effects of sympathetic nervous system (SNS) activation, induced via acute exercise, on sexual arousal in women was studied. In 2 experimental sessions, 36 women viewed a neutral film followed by an erotic film. In 1 session, the women were exposed to 20 min of intense exercise before viewing the films. Twelve women were sexually functional, 12 experienced significant impairments in sexual desire, and 12 experienced primary or secondary anorgasmia. Acute exercise significantly increased vaginal pulse amplitude (VPA) and vaginal blood volume (VBV) responses to an erotic film among sexually functional women and those with low sexual desire. Among anorgasmic women, exercise significantly decreased VPA but had no effect on VBV responses to an erotic film. Acute exercise had no significant effect on the women's perceptions of sexual arousal. Results suggest that increased SNS arousal may affect physiological sexual responding in women.

The effects of sympathetic activation on physiological and subjective sexual arousal in women

This investigation was designed to examine the effects of acute exercise on physiological and subjective sexual arousal in women. In Experiment 1, Ss participated in two experimental sessions in which they viewed a neutral film followed by an erotic film. In one of these sessions, Ss were exposed to 20 min of intense exercise prior to viewing the films. Subjective sexual arousal was measured with a self-report rating scale and physiological sexual arousal was measured with a vaginal photoplethysmograph. Acute exercise significantly decreased vaginal pulse amplitude responses to a neutral stimulus and significantly increased vaginal pulse amplitude responses to an erotic stimulus. Exercise marginally increased vaginal blood volume responses to an erotic film but had no significant effect on subjective perceptions of sexual arousal. In Experiment 2, Ss viewed two consecutive neutral stimuli preceded by 20 min of intense exercise. There were no significant differences in either vaginal blood volume or vaginal pulse amplitude between the two neutral films. Together, the data from Experiments 1 and 2 provide indirect support for a facilitatory role of sympathetic activation in female sexual arousal.

Inhibition of nitric oxide synthesis augments centrally induced sympathetic coronary vasoconstriction in cats

The principal effect of sympathetic activation on the coronary circulation is an alpha-adrenergic coronary vasoconstriction in the presence of beta-receptor blockade. Secondary effects include vasodilation due to beta-adrenoceptor stimulation and alpha 2-mediated release of endothelium-derived relaxing factor (EDRF) from the coronary vascular endothelium. We hypothesized that blockade of nitric oxide synthesis (nitro-L-arginine methyl ester, L-NAME) would augment coronary vasoconstriction to sympathetic stimulation as a result of a decrease in alpha 2-mediated EDRF release. In chloralose-anesthetized cats, hypothalamic stimulation produced increases in coronary vascular resistance [maximum 26 +/- 9% (SE)] and arterial pressure (41 +/- 7%) and a decrease in coronary blood flow velocity (15 +/- 6%). L-NAME (3 mg/kg iv) increased baseline arterial pressure from 69 +/- to 92 +/- 7 mmHg (P < 0.05). After L-NAME, a greater increase in coronary vascular resistance (55 +/- 20%, P < 0.05), a decrease in coronary blood flow velocity (24 +/- 7%, P < 0.05), and a similar pressor response (34 +/- 7%) were observed in response to hypothalamic stimulation. L-Arginine reversed the effect of L-NAME on coronary vasoconstriction to hypothalamic stimulation. Similar increases in arterial pressure (from 73 +/- 3 to 91 +/- 5 mmHg, P < 0.05) with vasopressin (0.01-0.05 U/min) failed to enhance coronary vasoconstriction to activation in anterior hypothalamus. We conclude that inhibition of EDRF synthesis augments centrally induced sympathetic coronary vasoconstriction in the cat.

Why does pulmonary venous pressure rise after onset of LV dysfunction: a theoretical analysis.

One of the most important consequences of acute left ventricular dysfunction (LVD) is pulmonary edema resulting from a rise in pulmonary venous pressure (PVP). It is generally believed that the PVP rise is a direct hemodynamic consequence of LVD. While this paradigm seems plausible, especially if the LV is viewed as a sump pump, there is no specific evidence to support this simple explanation. A theoretical analysis was performed to assess the hemodynamic mechanisms responsible for the dramatic rise in PVP after acute LVD. The ventricles were modeled as time-varying elastances; pulmonary and systemic vascular systems were modeled as series of resistive and capacitive elements. In response to a 50% decrease in LV contractile strength [end-systolic elastance (Ees)], cardiac output (CO) and mean arterial pressure (MAP) dropped substantially, while PVP increased minimally from its baseline of 12 to approximately 15 mmHg. With LV Ees set at 50% of normal, the effects of sympathetic activation were tested. When heart rate and total peripheral resistance were increased, CO and MAP improved, yet PVP still did not rise. The only intervention that caused a substantial increase in PVP was to simulate the decrease in unstressed volume (VU) of the venous system known to occur with sympathetic activation. When VU was decreased by about 15-20% (comparable to experimentally observed shifts with acute heart failure), PVP increased above 25 mmHg. The effects of pericardial constraints were investigated, and the results suggest a major role of this organ in determining the overall hemodynamic response to acute LVD, sympathetic activation, and explaining the responses to therapy. Thus this analysis suggests that elevations of PVP do not occur simply as a direct hemodynamic consequence of acute LVD. Rather, changes in PVP may be dictated more by sympathetic control on venous capacity. If confirmed, recognition of this as a primary mechanism may prove important in directing development of new therapies and in understanding the mechanisms of disease progression in heart failure.

Cardiac sympathetic nerve stimulation enhances cardiovascular performance during hyperkalaemia in the anaesthetized pig

A rapid increase in arterial plasma potassium concentration to values seen during intense exercise depresses cardiac function at rest. Increasing the cardiac concentration of noradrenaline by right-sided sympathetic stimulation in eleven anaesthetized pigs significantly augmented cardiovascular performance during hyperkalaemia, while electrical pacing of the right atrium at equivalent rates to sympathetic stimulation afforded no protection against the deleterious effects of hyperkalaemia. We conclude that the inotropic effect of sympathetic activation may be important in sustaining cardiac function during exercise-induced hyperkalaemia.