Role of cardiac mass in spontaneous defibrillation

Department of Normal Physiology, N. I. Pirogov Second Moscow Medical Institute. Institute of General Resuscitation, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. A. Negovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 10, pp. 339–340, October, 1991.     

Sympathetic nervous control of the cerebral circulation in sleep

Cerebral vessels are extensively innervated by sympathetic nerves arising from superior cervical ganglia, and these nerves might play a protective role during the large arterial pressure surges of active sleep (AS). We studied lambs (n=10) undergoing spontaneous sleep-wake cycles before and after bilateral removal of the superior cervical ganglia (SCGx, n=5) or sham ganglionectomy (n=5). Lambs were instrumented to record cerebral blood flow (CBF, flow probe on the superior sagittal sinus), carotid arterial pressure (P(ca)), intra-cranial pressure (P(ic)), cerebral perfusion pressure (Pcp=Pca-Pic) and cerebral vascular resistance (CVR). Prior to SCGx, CBF (mL min-1) was significantly higher in AS than in Quiet Sleep (QS) and Quiet Wakefulness (QW) (17+/-2, 13+/-3, and 14+/-3 respectively, mean+/-SD, P<0.05). Following SCGx, baseline CBF increased by 34, 31, and 29% respectively (P<0.05). CVR also decreased in all states by approximately 25% (P<0.05). During phasic AS, surges of Pca were associated with transient increases in Pcp, Pic and CBF. Following SCGx, peak CBF and Pic during surges became higher and more prolonged (P<0.05). Our study is the first to reveal that tonic sympathetic nerve activity (SNA) constricts the cerebral circulation and restrains baseline CBF in sleep. SNA is further incremented during arterial pressure surges of AS, limiting rises in CBF and Pic, possibly by opposing vascular distension as well as by constricting resistance vessels. Thus, SNA may protect cerebral microvessels from excessive distension during AS, when large arterial blood pressure surges are common.     

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.     

Sympathetic nerve activity in metabolic control – some basic concepts

A role for the sympathetic nervous system in hypertension has been looked for in relation to the ‘metabolic syndrome’ with associations between body weight, insulin sensitivity and hypertension. By use of microneurography human sympathetic responses to hypoglycaemia, normoglycaemic hyperinsulinaemia and food intake have been studied. A strong but differentiated influence of insulin‐induced hypoglycaemia comprises increase in muscle sympathetic nerve activity (MSNA) and the sudomotor part of skin sympathetic nerve activity (SSNA), whereas vasoconstrictor SSNA is inhibited. Responses to infusion of 2‐deoxy‐d ‐glucose are identical, suggesting central nervous system glucopenia and not insulin to be the causative factor. Insulin infusion during normoglycaemia evokes a moderate increase in MSNA; SSNA and blood pressure does not change. After glucose ingestion MSNA displays a sustained increase, which is only partly elicited by insulin. A significant albeit weaker increase occurs after pure protein or fat meals, and after glucose ingestion in C‐peptide‐negative diabetic patients, with no insulin secretion. In healthy elderly people the MSNA response to food intake is weak, because of a high outflow already at rest; this is suggested to explain postprandial hypotension in the elderly, a paradoxical mechanism behind clinical autonomic failure. A pathophysiological role of MSNA in the metabolic syndrome with hypertension has been speculated. An association between obesity and elevated level of MSNA at rest is established; observed relationships to chronic insulin levels and hypertension are less unanimous. The adipous tissue regulating hormone leptin has become one focus of interest in ongoing attempts to elucidate a possible role of the human sympathetic nervous system in the ‘metabolic syndrome’ and hypertension.     

Stress,the Sympathetic Nervous System and Hypertension

Abstract

Stress may be an important contributor to the pathogenesis of idiopathic (essential) hypertension. The probable pathway involves activation of the sympathetic nervous system and thereby an increase in peripheral resistance. This paper reviews the hemodynamics of early hypertension and attempts to relate them to stress-mediated overactivity of the sympathetic nervous system. Attention is also given the relations between obesity, race, sex and geography to hypertension.     

The influence of sleep onset on the diurnal variation in cardiac activity and cardiac control

Heart rate (HR), blood pressure (BP) and autonomic nervous system (ANS) activity vary diurnally, with a reduction in HR and BP, and a shift to vagal dominance during the dark phase. However, the cause of these changes, particularly the relative influence of sleep and circadian mechanisms, remains uncertain. The present study assessed the effect of sleep onset on HR, BP, high frequency (HF) component of heart rate variability (HRV), low frequency/high frequency (LF/HF) ratio and pre-ejection period (PEP). Sleep onset was dissociated from circadian influences by having subjects go to sleep at two different circadian phases, their normal time of sleep onset (normal sleep onset, NSO), and after a delay of 3 h (delayed sleep onset, DSO). The assumption was that changes caused by sleep onset would occur in association with sleep onset, irrespective of its timing, while circadian effects would have a consistent circadian phase and be independent of when sleep onset occurred. Thirteen and 17 subjects were run in the NSO and DSO conditions, respectively. Following a 1-h adaptation period, data collection began 2 h before subjects' normal time of sleep onset and continued until morning awakening. The lights were turned out after 2 h in the NSO condition and 5 h in the DSO condition. Subjects were required to maintain a supine position throughout the experimental sessions. The night-time decrease in HR was found to be due to both sleep onset and a circadian influence, with the circadian component being more prominent. In contrast, the fall in BP was largely due to a sleep onset effect. Increased vagal activity, as reflected in the HF component and a shift to vagal dominance in the LF/HF ratio, appeared to be primarily a function of the sleep system, while sympathetic activity, as assessed by PEP, reflected a circadian influence.     

Differential Distribution of Renal Nerves in the Sympathetic Ganglia of the Rat

The renal nerve plexus comprises efferent and afferent fibers. It controls urine production and bodily fluid homeostasis. Efferent fibers to the kidney include sympathetic nerve fibers from their main ganglia, the prevertebral suprarenal ganglia (SrG), and the paravertebral sympathetic chain ganglia (ChG). In the present study, we examined topological innervation from these ganglia to the renal parenchymal segments of the left kidney of the rat. Fluoro‐Gold was injected into the rostral or caudal poles of the left kidney. Approximately 50% of the cells in the SrG of rats injected in the rostral pole were labeled, while 60% of the cells in the ChG T13 of rats injected in the caudal pole were labeled. In addition, we performed dual‐probe retrograde tracing of the nerves using two kinds of fluorescent‐conjugated cholera toxins (f‐CTbs) injected into the rostral and caudal poles of the left kidney. The cells labeled with each f‐CTb were distributed differently in the left SrG and the lower ChGs; no dual‐labeled cells were found in these ganglia. Anterograde tracing with pCAGGS‐tdTomato vector transfected into the left SrG showed that tdTomato‐labeled nerve varicosities extended to the cortical arterioles and urinary tubules. Immunohistochemistry revealed that they were positive to tyrosine hydroxylase and synaptophysin, suggesting that they possessed sympathetic nerve endings. Our results show that renal efferent nerves in the SrG may control the rostral part of the kidney and innervate the multiple effectors in the cortex. Anat Rec, 300:2263–2272, 2017. © 2017 Wiley Periodicals, Inc.     

Studies on the Activity of the Sympathetic Nervous System in Essential Hypertension

Abstract

Plasma catecholamine and norepinephrine concentrations have been measured in carefully characterized ambulatory patients with essential hypertension under basal conditions and following experimental procedures known to enhance sympathetic activity. The studies have demonstrated increased levels of plasma catecholamines in patients with mild hypertension as compared with matched controls following 70° upright tilt or cold pressor testing. Considerable heterogeneity was apparent in the population of patients with essential hypertension with respect to their plasma norepinephrine concentrations. Significantly greater levels of plasma norepinephrine were present in patients with high plasma renin activity and lesser levels in patients with low renin activity than in normal renin or labile hypertensives. Blood pressure correlated significantly with plasma norepinephrine in male patients with normal renin essential hypertension but not in females. Administration of the diuretic furosemide produced an increase in plasma norepinephrine in almost all hypertensive subjects studied.

These studies suggest that peripheral sympathetic activity is abnormal in certain patients with essential hypertension. The results underscore the need to differentiate between subgroups of essential hypertension in studies relating to the role of the adrenergic system in the hypertension. The findings also suggest that the recently developed sensitive techniques for measuring plasma catecholamines or plasma norepinephrine are of value in assessing changes in peripheral sympathetic activity but that enzymatic assays of serum dopamine-beta-hydroxylase activity are probably not useful for this purpose.     

大鼠部分后根损伤诱发机械性痛性感觉异常的交感神经依赖性

建立一个类似临床的后根损伤诱发慢性痛的动物模型,探讨交感神经活动在诱发慢性痛中的作用。在腰5 部分后根结扎损伤的方法建立一个后根损伤大鼠模型,观察损伤诱发的慢性痛形成的行为和电生理学特征及交感节后神经元在慢性痛形成中的作用。结果表明：（1） 腰5 部分后根结扎损伤后,损伤侧后肢出现机械性痛性感觉异常,持续约30 天。（2）提前12 天行腰交感神经干和神经节切除术,部分后根损伤侧后肢不出现机械性痛性感觉异常。（3） 腹腔注射肾上腺素能a 受体阻断剂酚妥拉明（4mg/kg）使机械性痛性感觉异常显著降低,维持约30min。（ 4）后根的部分损伤诱发损伤神经21.7%（162/746）的A 类纤维来自背根节细胞的异位放电活动;全身或局部应用去甲肾上腺素可使异常自发电活动产生改变,其中64.1%的（25/39）A 类纤维兴奋,33.3%（13/390 的A 类纤维抑制。提示交感神经参与后根损伤诱发的机械性痛性感觉异常。     

Autonomic nervous control of the heart rate response to dynamic incremental exercise: evaluation of the Rosenblueth-Simeone model

Summary To evaluate the validity of the Rosenblueth-Simeone model for the heart rate response to incremental dynamic exercise, 11 healthy men performed maximal exercise tests on a cycle ergometer after administration of placebo, propranolol, atropine or both propranolol and atropine. The model showed that the influence of sympathetic activity on heart rate increased at intensities up to those which resulted in a heart rate 70% maximal heart rate on placebo, and levelled off at higher intensities, while there was a progressive withdrawal of the parasympathetic activity. The ratio between heart rate predicted by the model and the recorded heart rate following placebo treatment tended to be less than 1.0 at lower exercise intensities, and approached the unit at intensities above those which resulted in a heart rate higher than 70% of maximal heart rate on placebo. There was a strong correlation (r=0.94,P<0.01) between the heart rate on placebo and the heart rate estimated by the model. Nevertheless, there was some scattering of the data around the identity line, with a standard error of the estimate for the regression line of 11 beats · min^–1. Thus, during incremental exercise, the influence of sympathetic activity on heart rate does not become progressively more important at higher exercise intensities. The application of the Rosenblueth-Simeone model shows limitations during incremental exercise, particularly at low exercise intensities.     

Tone of Sympathetic Nerves and Regulation of Heart Activity

Tone of sympathetic nerves to the heart was studied in rats and guinea pigs. Experiments with pharmacological blockade of the sympathetic nervous system and vagotomy confirmed the general notion on the absence of tonic effects of sympathetic nerves on the heart. Reduction of the heart rate reported previously probably attests to various experimental designs (type and depth of anesthesia, possible hypothermia, duration of observations, and pharmacological preparations). As differentiated from the vascular tone, the heart rate under rest conditions depends on the vagal tone and circulating humoral substances.     

Parasympathetic control of the spontaneous defibrillation of the heart ventricles in animals of various ages

The role of the parasympathetic division of the nervous system in the process of the spontaneous defibrillation of the heart ventricles in guinea pigs of various ages has been investigated. It was shown that the intensification of parasympathetic control in newborn and sexually mature animals by means of the stimulation of the vagus nerves through the administration of acetylcholine leads to an increase in the duration of ventricular fibrillation, while in old animals this leads to the possibility of its prevention. The important role of the maintenance of sympathetic control in the mechanisms of the recovery of normal cardiac rhythm has been demonstrated.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 76, No. 2, pp. 207–212, February, 1990.     

Sympathetic Withdrawal Augments Cerebral Blood Flow During Acute Hypercapnia in Sleeping Lambs

Study Objectives:

Cerebral sympathetic activity constricts cerebral vessels and limits increases in cerebral blood flow (CBF), particularly in conditions such as hypercapnia which powerfully dilate cerebral vessels. As hypercapnia is common in sleep, especially in sleep disordered breathing, we tested the hypothesis that sympathetic innervation to the cerebral circulation attenuates the CBF increase that accompanies increases in PaCO₂ in sleep, particularly in REM sleep when CBF is high.

Design:

Newborn lambs (n = 5) were instrumented to record CBF, arterial pressure (AP) intracranial pressure (ICP), and sleep-wake state (quiet wakefulness (QW), NREM, and REM sleep). Cerebral vascular resistance was calculated as CVR = [AP-ICP]/CBF. Lambs were subjected to 60-sec tests of hypercapnia (FiCO₂ = 0.08) during spontaneous sleep-wake states before (intact) and after sympathectomy (bilateral superior cervical ganglionectomy).

Results:

During hypercapnia in intact animals, CBF increased and CVR decreased in all sleep-wake states, with the greatest changes occurring in REM (CBF 39.3% ± 6.1%, CVR −26.9% ± 3.6%, P < 0.05). After sympathectomy, CBF increases (26.5% ± 3.6%) and CVR decreases (−21.8% ± 2.1%) during REM were less (P < 0.05). However the maximal CBF (27.8 ± 4.2 mL/min) and minimum CVR (1.8 ± 0.3 mm Hg/ min/mL) reached during hypercapnia were similar to intact values.

Conclusion:

Hypercapnia increases CBF in sleep and wakefulness, with the increase being greatest in REM. Sympathectomy increases baseline CBF, but decreases the response to hypercapnia. These findings suggest that cerebral sympathetic nerve activity is normally withdrawn during hypercapnia in REM sleep, augmenting the CBF response.

Citation:

Cassaglia PA; Griffiths RI; Walker AM. Sympathetic withdrawal augments cerebral blood flow during acute hypercapnia in sleeping lambs. SLEEP 2008;31(12):1729–1734.     

Sympathetic regulation of fructose secretion in the seminal vesicle of the guinea-pig

Fructose secretion of everted guinea-pig seminal vesicles was studied in vitro. Carbachol produced dose dependent increase in fructose secretion. The effect was blocked by scopolamine but not by hexamethonium, mecamylamine, tetrodotoxin or previous denervation. High concentrations of acetylcholine also increased fructose secretion. This response was not augmented by physostigmine. Methoxamine reduced secretion. Methoxamine, terbutaline, clonidine and vasoactive intestinal peptide counteracted carbachol. Field stimulation produced increased secretion that was not blocked by autonomic drugs, tetrodotoxin or previous denervation. Stimulation of the hypogastric nerve produced frequency dependent increase in fructose secretion. The effect was blocked by tetrodotoxin and scopolamine but not enhanced by physostigmine. If the hypogastric nerve was stimulated close to the seminal vesicle the response was unaffected by hexamethonium but proximal stimulation was blocked. After chronic proximal denervation of the hypogastric nerve, stimulation close to the seminal vesicle produced enhanced response. Destruction of the peripheral ganglia at the base of the seminal vesicle abolished the response. Sections showed that most secretory nervesenter the organ at its base. Phentolamine or yohimbine but not prazosine or propranolol or guanethidine enhanced the secretory response to distal hypogastric nerve stimulation. Tyramine counteracted the response but after reserpinization it was enhanced by tyramine. It is concluded that the secretory cells of the guinea-pig seminal vesicle have a sympathetic secretomotor innervation by short cholinergic neurones with a preganglionic supply via the hypogastric nerve. Inhibitory α₁ and β₂-adrenoreceptors are present on the cells but neurogenic adrenergic inhibition of the secretion is essentially prejunctional and due to activation of inhibitory α₂-receptors on the secretomotor nerves.     

Sympathetic ANS modulation of pupil diameter in emotional scene perception: Effects of hedonic content,brightness, and contrast

A series of studies investigated the effects of hedonic content, brightness, and contrast on pupil diameter during free viewing of natural scenes, assessing the amplitude of the initial light reflex and subsequent sustained pupil diameter change. Hedonic picture content varied from highly arousing scenes of erotica and violence to scenes depicting nature, babies, loss, contamination, food, and more. Despite equivalent overall picture brightness and contrast, pupil diameter still varied as a function of the local brightness of central vision at fixation. Statistical (Experiment 1) and methodological (Experiment 2, 3) solutions produced complementary data indicating that scenes of erotica and violence reliably attenuate the amplitude of the initial light reflex and prompt enhanced late diameter pupil changes, compared to other scene contents. A principal components analysis supported the hypothesis that a single sympathetically mediated process enhances pupil dilation during picture viewing, modulating both initial constriction and late diameter changes. Rather than being a subtle index of “liking,” pupil diameter is primarily sensitive to events that reliably elicit measurable sympathetic nervous system activity.     

Cardiovascular response to exercise in humans following acclimatization to extreme altitude

The purpose of this study was to assess the effects of acclimatization to extreme altitude on the cardiovascular system, using vagal and adrenergic blockade and acute restoration of normoxia during exercise to maximum with one and two legs. Fourteen climbers on an expedition to the Himalayas were studied at a lower base camp (5250 m) following 56–81 days at altitudes between 5250 and 8700 m. After acclimatization, peak heart rate (HR_peak), oxygen uptake (o_2k) and noradrenaline (NA) were similar during maximal one- and two-legged cycling, whereas peak plasma lactate was higher during the one-legged protocol. HR_peak (range 113–168 beats min“¹) was lowest when subjects returned from the higher camps. The degree of partial restoration of HR_peak to more normal values within seconds of 60% 0₂ inhalation (range 5–35 beats min?^l HR_peak increase) was greatest in subjects with low HR_peak. HR responses to /?-l blockade increased as a function of HR_peak and the HR responses to atropine were the least in subjects with high HRpeak- These findings suggest that (a) the reduction in HR_peak is linked to the duration and severity of the hypoxaemia, (b) the degree of restoration of HR_peak with acute normoxia is dependent on the level of attenuation or down-regulation of cardiac sympathetic activation (SNA), (c) cardiac vagal drive is masked to a lesser extent in chronic hypoxia because of attenuated SNA and lower HR_peak values, and (d) the lower blood lactate levels at altitude is a function of muscle mass involvement rather than adrenergic activation, as normal peak values were reached during exercise with a small muscle mass.     

Optimal parameters of electrical defibrillation of the atria

In acute experiments on dogs thoracotomy was performed and atrial flutter and fibrillation induced. The threshold levels of current, energy, and charge required to abolish these arrhythmias were determined in the case of direct application of a monopolar square pulse ranging in duration from 1 to 15 msec were determined. The values of the current and energy defibrillating the atria when the electrodes were applied directly to them were minimal if the duration of the pulse was 8 msec: 113±13.7 mA and 10.4±2.6 mW·sec, respectively, to abolish flutter and 275±18.2 mA and 62.3±9.0 mW·sec to abolish fibrillation. The strength of the current restoring the nomotopic rhythm by direct strial defibrilation was only one-fiftieth of the strength of the current previously established for transthoracic atrial defibrillation in dogs. The effectiveness of direct atrial defibrilation under experimental conditions points to the need for development of an adequate method for its clinical application.Laboratory of Experimental Cardiology, P. K. Anokhin Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 4, pp. 397–400, April, 1978.