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![Effects of congestive heart failure (CHF; due to pacing) on mean arterial pressure (MAP) heart rate (HR), left atrial pressure (LAP), and plasma norepinephrine concentration (Plasma NE) in 9 intact and 9 sinuaortic denervated (SAD) conscious dogs. *: P < 0.05 CHF versus control. ....: P < 0.05 SAD versus control [Redrawn from data in (9)]](profile/Hartmut-Kirchheim/publication/13453922/figure/fig3/AS:601589131800632@1520441434989/Effects-of-congestive-heart-failure-CHF-due-to-pacing-on-mean-arterial-pressure-MAP.png)
Effects of congestive heart failure (CHF; due to pacing) on mean arterial pressure (MAP) heart rate (HR), left atrial pressure (LAP), and plasma norepinephrine concentration (Plasma NE) in 9 intact and 9 sinuaortic denervated (SAD) conscious dogs. *: P < 0.05 CHF versus control. ....: P < 0.05 SAD versus control [Redrawn from data in (9)]
Source publication
This review deals with the neuro-hormonal changes in congestive heart failure, a syndrome that is usually initiated by a reduction of cardiac output. In order to do this, we should like to 1) summarise previous and more recent evidence for a number of these neuro-hormonal derangement’s, 2) review the experimental evidence for an abnormality in the...
Contexts in source publication
Context 1
... the cardiovascular reflexes and the neur-hormonal changes should be mentioned (9). The authors looked for the changes in plasma norepi- nephrine in chronically sinuaortic denervated dogs in which heart failure was induced by rapid pacing. They found that without sinuaortic receptors there was still a significant increase in plasma norepinephrine (Fig. 3). Unfortunately this does not exclude that a possible defect in the remaining car- diopulmonary receptors was responsible for the increase in plasma noradrenaline in heart ...
Context 2
... normal rats, it restored the reduced gain in congestive heart failure to reach 80 % of that observed in the control rats. Although it should be considered that renal sympathetic nerve discharge for methodological reasons had to be plotted in % of control, a comparison of the function curves in congestive heart failure before and after losartan in Fig. 3 of the study even suggests some resetting. However, the most important finding in the study was that losartan adminis- tration to conscious rats with heart failure decreased renal sympathetic nerve discharge at an unchanged arterial blood pressure ...
Citations
... The current study is in line with previous observations (6,22,34,54,75) and demonstrates elevated cardiac sympathetic tone and attenuated parasympathetic tone in conscious HF rats, Values are means Ϯ SE; n ϭ 7. EDP, end-diastolic pressure; ESV, end-systolic volume; EDV, end-diastolic volume; SV, stroke volume; EF, ejection fraction; CO, cardiac output; ϩdP/dt and ϪdP/dt, maximal slope of the systolic increment and diastolic decrement of ventricular pressure, respectively; , relaxation time constant; HF, heart failure; PYR, pyridostigmine. *P Ͻ 0.05 compared with the control group; †P Ͻ 0.05 compared with the HF group. ...
Heart failure (HF) is characterized by elevated sympathetic activity and reduced parasympathetic control of the heart. Experimental evidence suggests that the increase in parasympathetic function can be a therapeutic alternative to slow HF evolution. The parasympathetic neurotransmission can be improved by acetylcholinesterase inhibition. We investigated the long term (four weeks) effects of the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance, cardiac remodeling and cardiac function in the onset of HF following myocardial infarction. Myocardial infarction was elicited in adult male Wistar rats. After four weeks of pyridostigmine administration, per os, methyl-atropine and propranolol were used to evaluate the cardiac sympathovagal balance. The tachycardic response caused by methyl-atropine was considered to be the vagal tone, while the bradycardic response caused by propranolol was considered to be the sympathetic tone. In conscious HF rats, pyridostigmine reduced the basal heart rate, increased vagal and reduced sympathetic control of heart rate. Pyridostigmine reduced the myocyte diameter and collagen density of the surviving left ventricle. Pyridostigmine also increased vascular endothelial growth factor protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac function was assessed by means of the pressure-volume conductance catheter system. HF rats treated with pyridostigmine exhibited a higher stroke volume, ejection fraction, cardiac output and contractility of the left ventricle. It was demonstrated that the long term administration of pyridostigmine started right after coronary artery ligation augmented cardiac vagal and reduced sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction during the progression of HF in rats.
... Wie referiert und gezeigt, sind weder Behandlungsansatz noch die Methode neu, aber dank neuerer Technologie und einer seriösen klinischen Entwicklung steht ein Implantat zur chronischen Reizung barorezeptorischer Afferenzen zur Verfügung, das physiologische Mechanismen der Blutdruckregulation nutzen kann. Zur zentralnervösen Regulation des Blutdrucks kann auf Übersichten verwiesen werden [41,42]. ...
tienten haben gezeigt, dass auch nach 12 Mo- naten der systolische Blutdruck im Mittel um mehr als 25 mmHg nachhaltig reduziert war, wobei die medikamentöse Begleittherapie un- verändert war. Es wurden keine unerwarteten schwerwiegenden unerwünschten Ereignisse berichtet, so dass sich diese neue Methode als Alternative bei Patienten mit schlechter Prog- nose unter stark hypertensiven Blutdruckwerten eignet. Die Risikobewertung hat insbesondere perioperative Risiken wie Infektionen und Ver- letzungen zu berücksichtigen. Allerdings könnte diese neue Therapie trotz einer notwendiger- weise konservativen Risikobewertung einen Bei- trag zur künftigen Behandlung von vielen "unkon- trollierten" Hochdruckpatienten leisten, insbeson- dere auch dann, wenn die medikamentöse The- rapie schlecht vertragen wird. Abstract: Therapeutic Reduction of Blood Pressure Using an Active Implantable De- vice: A New Method to Treat Drug Treat- ment-Refractory Hypertension. When com- pliant hypertensive patients are uncontrolled and refractory to a combination regimen of at least 3 drugs without a treatable secondary cause, a new device-based treatment under develop- ment may be indicated. This review deals with the development and early safety and efficacy data of an active implantable device for the chronic electrical stimulation of baroreceptor-af- ferent nerve fibres in the vessel wall of the ca- rotid artery bifurcation. Although the principle of such a treatment has been known for a long time, a new device is being developed which is fully implantable similar to a cardiac defibrilla- tor and can be programmed to deliver electrical stimulation impulses to both carotid bifurca- tions. Early data with a positive benefit vs risk assessment from 2 clinical studies (in Europe and the USA) led to certification with the CE mark in 2007, i. e. the approval of marketing in Europe. By the end of 2007, more than 60 pa- tients were treated with the device in the con- text of clinical studies. Long-term data are avail- able in a limited number of patients and have shown sustained systolic blood pressure reduc- tions of more than 25 mmHg after 12 months of treatment. No unexpected serious adverse events have been reported so far. Considering this new treatment as an alternative in patients with a poor prognosis when remaining severely hyper- tensive has to take into regard operative risks such as infections and injury. Despite such a conservative risk assessment, this new treat- ment might contribute to the future treatment of many currently uncontrolled patients. J Hyper- ton 2008; 12 (3): 22-7.
... Details have been described and reviewed in the literature (see Refs [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] for groups 1 and 2 and Refs [24][25][26] for group 3). ...
The sympathetic nervous system is involved in many autonomic regulations leading to homeostasis and adaptation of the homeostatic regulations to the internal and external demands on the body. The basic peripheral building blocks of these regulations are the final sympathetic pathways, consisting of populations of pre- and postganglionic neurons that are functionally defined according to the effector cells they supply (vascular smooth muscle cells, non-vascular smooth muscle cells, secretory epithelia, etc.).
... Together these observations suggest that the NOSinhibitor-induced bradycardia is primarily a manifestation of the activity of n-NOS in vagal neurons of the brain, and therefore should be characterized by a particular dose-effect relationship. To test this hypothesis we determined the effects of N--nitro-arginine-methylester (L-NAME), a nonselective NOS inhibitor, on heart rate and heart rate variability as a measure of vagal activity (22,46) as well as on vascular flow resistance as a measure of vasomotor tone in a placebo-controlled study on awake dogs. These experiments will show for the first time that the dose-dependent bradycardia occurs in parallel with vagal activation at smaller doses of L-NAME than those which cause vasoconstriction. ...
Nitric oxide synthase (NOS) inhibitors elicit bradycardias independent of the endothelium (e-NOS) or increases in blood pressure. Therefore, this bradycardia could be mediated by other NOS isoforms, most likely that of the nervous system (n-NOS). If so, heart rate variability (HRV) as a measure of vagal activity should be an indicator of the activity of n-NOS in vagal neurons. To test this, we studied the dose-effect relations of L-NAME (0.3 - 50 mg x kg(-1)) on heart rate (HR), HRV and systemic vascular resistance (SVR) in seven awake dogs. HRV was analyzed in the time domain as standard deviation of the RR-intervals (SDNN) and in the frequency domain as power in the high (0.15 - 0.5 Hz) and low (0.04 - 0.15 Hz) frequency range. The effects of HR and SDNN reached their maxima at a dose of 3 mg x kg(-1) and had their ED50 at 0.27 +/- 0.03 mg x kg(-1) and 0.43 +/- 0.1 mg x kg(-1), respectively, whereas SVR had its maximum at 10 mg x kg(-1) and ED50 at 0.86 +/- 0.11 mg x kg(-1) (p < 0.05). HF-power (vagal activity) predominated compared to LF-power (mainly sympathetic activity) during baseline as well as after L-NAME. The effects on HR and HRV were absent after ganglionic blockade (hexamethonium), whereas the effects on SVR remained unchanged. Thus, NO exerts a powerful restraining activity on vagal neurons and plays a key role in the adjustment of heart rate in awake resting animals with prevailing vagal activity.
When compliant hypertensive patients are uncontrolled and refractory to a combination regimen of at least 3 drugs without a treatable secondary cause, a new device-based treatment under development may be indicated. This review deals with the development and early safety and efficacy data of an active implantable device for the chronic electrical stimulation of baroreceptor-afferent nerve fibres in the vessel wall of the carotid artery bifurcation. Although the principle of such a treatment has been known for a long time, a new device is being developed which is fully implantable similar to a cardiac defibrillator and can be programmed to deliver electrical stimulation impulses to both carotid bifurcations. Early data with a positive benefit vs risk assessment from 2 clinical studies (in Europe and the USA) led to certification with the CE mark in 2007, i. e. the approval of marketing in Europe. By the end of 2007, more than 60 patients were treated with the device in the context of clinical studies. Long-term data are available in a limited number of patients and have shown sustained systolic blood pressure reductions of more than 25 mmHg after 12 months of treatment. No unexpected serious adverse events have been reported so far. Considering this new treatment as an alternative in patients with a poor prognosis when remaining severely hypertensive has to take into regard operative risks such as infections and injury. Despite such a conservative risk assessment, this new treatment might contribute to the future treatment of many currently uncontrolled patients.
Sympatho-excitation is a hallmark of the chronic heart failure (CHF) state. It has long been assumed that this sympatho-excitation is mediated by a reduction in sensory input from cardiopulmonary and arterial baroreceptors. However, recent data suggest that these reflexes may only be important in the initiation of the sympatho-excitatory state and may not be necessary for the sustained increase in sympathetic nerve activity (SNA) in CHF. Two humoral factors that can influence SNA are nitric oxide (NO) and angiotensin II (AngII). Animals with CHF exhibit a downregulation in central gene expression for the neuronal isoform of nitric oxide synthase (nNOS). In addition, blockade of AngII receptors in combination with NO donation reduces SNA in animals with CHF, while NO donation alone has no effect on SNA. Chronic exercise training (EX) reduces both plasma AngII and SNA in rabbits with CHF while improving baroreflex function. Blockade of AT1 receptors enhances baroreflex function in non-EX CHF rabbits, but has little effect in EX CHF rabbits. These data suggest that the sympatho-excitatory state that is typical of CHF is, in part, due to changes in AngII and NO. Depressed baroreflex function and the elevated SNA can be improved by EX in animals with CHF.
Almost all bodily functions are dependent on the functioning of the autonomic nervous system - from the cardiovascular system, the gastrointestinal tract, the evacuative and sexual organs, to the regulation of temperature, metabolism and tissue defence. Balanced functioning of this system is an important basis of our life and well-being. This book gives a detailed description of the cellular and integrative organization of the autonomic nervous system, covering both peripheral and central aspects. It brings to light modern neurobiological concepts that allow understanding of why the healthy system runs so smoothly and why its deterioration has such disastrous consequences. This academic reference volume will appeal to advanced undergraduate and graduate students studying the neurobiology of the autonomic nervous system within the various biological and medical sciences and will give access to ideas propagated in psychosomatic and alternative medicines.
Objective: To evaluate plasma sodium and glucose concentrations in dogs with congestive heart failure (CHF) prior to treatment and evaluate the differences between survivors and non‐survivors.
Design: Retrospective study.
Animals: Fifty‐nine dogs with CHF prior to receiving cardiac medication.
Interventions: None.
Measurements and main results: The mean plasma sodium concentration in dogs with CHF was below the reference range (144–156 mmol/L) and significantly lower ( P =0.009) in non‐survivors (141±6 mmol/L) compared with survivors (147±4 mmol/L). The mean plasma glucose concentration was above the reference range (76–117 mg/dL) and significantly higher ( P =0.004) in non‐survivors (128±52 mg/dL) compared with survivors (100±13 mg/dL). Forty‐four percent of non‐survivors had concurrent low plasma sodium and high plasma glucose concentrations, whereas no survivors had both abnormalities ( P <0.0001).
Conclusions: Lower plasma sodium and higher plasma glucose are associated with a worse outcome in dogs with CHF.
TASK-1, a member of the recently identified K2P channel family, is mainly expressed in the heart and the nervous system. TASK-1 is regulated by several physiological and pathological conditions and functions as a background potassium channel. However, there are limited data concerning the significance of TASK-1 in cardiac physiology. We studied the functional role of TASK-1 in the heart by cardiac phenotyping the TASK-1-deficient mouse (TASK-1(-/-)). TASK-1 was predominantly expressed in the ventricles of control animals. Real-time PCR and immunoblot demonstrated that the expression of seven other K2P channels was unchanged in TASK-1(-/-) mice. No structural or functional abnormalities were found by histology and echocardiography. Electrophysiological studies recording monophasic action potentials (MAPs) showed a significant prolongation of action potential duration in spontaneously beating and atrially paced hearts, respectively. Surface ECGs of TASK-1(-/-) mice revealed a significant prolongation of the rate corrected QT interval. Telemetric ECG recordings for 24 h, during physical and pharmacological stress testing and after ischemia/reperfusion injury did not result in a higher incidence of arrhythmias. Infarct size was comparable in both genotypes. However, TASK-1(-/-) mice had a higher mean heart rate and significantly reduced heart rate variability (HRV). Time and frequency domain measurements as well as baroreceptor reflex testing revealed a sympathovagal imbalance with a shift to an increase in sympathetic influence in TASK-1(-/-) mice. In conclusion, TASK-1 plays a functional role in the repolarization of the cardiac action potential in vivo and contributes to the maintenance of HRV.
