Cardiac Sympathetic Afferents Research Articles

Renal nerve and cardiovascular responses to cardiac receptor stimulation in rabbits.

It has been shown that a species difference exists among cats, dogs, and monkeys in the reflex response to cardiac sympathetic afferent stimulation with bradykinin (BK). This study was performed to determine the arterial blood pressure (ABP), heart rate (HR), and renal nerve activity (RNA) responses to epicardial BK applications in the intact and sinoaortic-denervated and vagotomized (SAD + Vx) rabbits. Eight rabbits were anesthetized with pentobarbital sodium. The heart was exposed and suspended in the epicardial cradle. The ABP, HR, and RNA responses were determined when 1 and 10 micrograms/ml BK were applied to the anterior surface of the left ventricle in the intact and SAD + Vx state. In both the intact and SAD + Vx rabbits, ABP, HR, and RNA were significantly reduced with epicardial BK. In the SAD + Vx rabbits, BK evoked small decreases in ABP and HR and no change in RNA after topical lidocaine. These results show the existence of a depressor response and decreases in HR and RNA in the rabbit mediated by the action of BK on cardiac sympathetic afferents.

Responses of feline medial medullary reticulospinal neurons to cardiac input.

1. Responses of medial medullary reticulospinal (RS) neurons to electrical stimulation of cardiac sympathetic afferents, probing the epicardium and epicardial application of bradykinin, were determined in cats anesthetized with alpha-chloralose. Conduction velocity of RS cells averaged 67 m/s; these neurons were probably part of the RS motor pathway and the bulbospinal pathway that modulates ascending information. Fifty-three RS neurons had unilateral projections and 18 neurons bilateral projections to the thoracic spinal cord. 2. Maximal electrical stimulation of the left stellate ganglion excited 69% of 97 RS neurons with a mean latency of 15 +/- 1.0 ms. Mean spike discharge rate increased from 4 +/- 1.2 to 93 +/- 8.0 spikes/s for responsive neurons. 3. Epicardial bradykinin (0.04 mg) excited 34%, inhibited 2%, and did not affect 64% of 44 RS cells tested. Excited neurons increased their mean discharge rate from 12.3 +/- 3.6 to 18.2 +/- 4.3 spikes/s, with a latency of 24 +/- 3.0 s, in response to bradykinin. Response duration averaged 43 +/- 2.3 s. Neurons responsive to bradykinin had greater spontaneous discharge rates than unresponsive neurons. Thirteen of 16 RS cells excited by bradykinin were located in the gigantocellular tegmental field (FTG); the other three cells were in the paramedian nucleus (PR). 4. Epicardial bradykinin often elicited changes in aortic pressure. Although some neurons responded to altered blood pressure alone, these responses could not account for responses to bradykinin. Furthermore, the percentage of responsive neurons was similar in experiments with intact nerves as well as those with vagotomy and barodenervation. 5. Touching the epicardium with a blunt probe excited 19 of 60 (32%) RS neurons, and visceral receptive fields were mapped for 12 of these cells. Neurons responded with one to three spikes to probing. RS neurons responsive to probing were scattered throughout the medial reticular formation. 6. RS cells were also tested for somatic, auditory, and visual input. Of 63 neurons responsive to sympathetic afferent stimulation, only one did not receive convergent input from at least one of these sources; 51% received input from each tested source. Neurons responsive to bradykinin were more likely to receive visual input than the general population of neurons. RS neurons unresponsive to sympathetic afferent stimulation were less likely to receive convergent inputs from other sensory modalities.(ABSTRACT TRUNCATED AT 400 WORDS)

Global versus regional myocardial ischaemia: differences in cardiovascular and sympathetic responses in cats.

The cardiovascular and sympathetic responses to occlusions of the left main ("global" ischaemia) or distal left anterior descending ("regional" ischaemia) coronary artery were studied in 19 anaesthetised cats with chronic sinoaortic baroreceptor denervation. "Global" ischaemia, before vagotomy, resulted in a significant reduction of mean arterial pressure (MAP), left ventricular pressure (LVP), and LVdP/dtmax while sympathetic efferent impulse activity was significantly augmented during the initial 15 +/- 2 s of occlusion (early phase) and, vice versa inhibited during the subsequent 20 +/- 2 s of occlusion (late phase). Vagotomy did not modify the haemodynamic responses, however, a significant increase in sympathetic discharge was detectable during the whole occlusion period (early and late phases). "Regional" ischaemia, before vagotomy, resulted in a significant increase in sympathetic neural discharge and MAP, with no changes in left ventricular function. After vagotomy the occlusion elicited a significant increase in MAP, LVP, LVdP/dtmax and efferent sympathetic neural activity. These excitatory responses were abolished after the interruption of a large part of the cardiac sympathetic afferents. Thus coronary artery occlusion induced haemodynamic and sympathetic reflex responses that were dependent upon the interaction of opposite influences mediated by the simultaneous activation of cardiac vagal and sympathetic afferents. The extent of "ischaemic myocardium" represented a determinant factor for the prevailing type of neural response.

Multisegmental spinal sympathetic reflexes originating from the heart.

Activation of cardiac sympathetic afferent nerves can initiate excitatory cardiocardiac reflexes through pathways that are exclusively spinal. In addition, stimulation of the same nerves also causes lower thoracic and lumbar sympathetic excitation, but the contribution of spinal pathways to these reflexes is unknown. Therefore experiments were performed to compare cardiac, splenic, and renal sympathetic responses to cardiac sympathetic afferent stimulation before and after cervical spinal cord transection in anesthetized, vagotomized, sinoaortic-denervated cats. Electrical stimulation of afferent cardiac sympathetic nerves produced excitatory responses in cardiac and renal nerves before transection but only cardiac nerve responses after transection. In contrast, afferent stimulation by epicardially applied bradykinin excited cardiac, renal, and splenic nerves before and after cord transection. Splenic nerve responses were greater than renal nerve responses in intact and spinal cats. These results demonstrate that spinal reflexes initiated by activation of cardiac sympathetic afferent nerves are not limited to cardiocardiac pathways. The similarity of patterns of responses in intact and spinal cats suggests that spinal pathways contribute significantly to the reflex excitation observed in intact animals.

Renal nerve responses to cardiac receptor stimulation with bradykinin in monkeys

Previous data from our laboratory demonstrated a species difference between the cat and dog in the arterial blood pressure (ABP) and renal nerve activity (RNA) responses to epicardial bradykinin (BK) applications. The present study was carried out to determine the ABP and renal nerve responses to chemical activation of cardiac afferents by BK in the intact and sinoaortic-denervated and vagotomized (SAD + VX) nonhuman primate. Seven Macaque monkeys (fascicularis and nemestrina) anesthetized with pentobarbital or chloralose were used in this study. The heart was exposed and suspended in a pericardial cradle. A left atrial (LA) catheter was inserted through the appendage. Changes in ABP and RNA (percent change from control) were determined when 1 and 10 micrograms/ml BK (in 1-ml volume) were applied to the anterior surface of the left ventricle or injected into the LA (0.3 and 3.0 micrograms/kg BK) in the intact and SAD + VX state. In both the intact and SAD + VX monkeys, ABP and RNA were significantly reduced with epicardial BK. In the intact state, LA injections of BK produced a significant decrease in the % delta of RNA and a depressor response. In the SAD + VX monkey, significant hypotensive responses were also observed with LA injections of BK concomitant with significant reductions in RNA. These results show the existence of a depressor response and inhibition of renal sympathetic nerve activity in the nonhuman primate mediated by the action of bradykinin on cardiac sympathetic afferents.

Cardiovascular reflexes mediated by sympathetic afferent fibers

In this paper the experimental evidence supporting the hypothesis that excitatory sympathetic reflexes may participate in the tonic control of the cardiovascular system is discussed. Positive feedback pressor sympathetic reflexes can be obtained with physiological distensions of the descending thoracic aorta in conscious dogs with all nerves intact in absence of any pain reaction. These excitatory reflexes interact with supraspinal regulatory mechanisms, inhibitory in nature. A massive excitation of cardiac sympathetic afferents, produced by intracoronary injections of bradykinin, also elicits a pressor reflex, without pain reactions. In the absence of anesthesia and recent surgery, the cardiovascular excitatory reflexes, subserved by sympathetic afferent fibers, can easily prevail. We suggest that negative and positive feedback mechanisms interact continuously to achieve the most adequate neural cardiovascular control.

Responses to activation of cardiac sympathetic afferents with epicardial bradykinin.

The cardiovascular reflex responses mediated by cardiac sympathetic afferent fibers (CSA) appear to differ depending on the nature of the activating stimulus. Although electrical stimulation of CSA may result in either excitatory of inhibitory reflex responses in both cats and dogs, topical application of bradykinin to these sensory endings elicits only excitatory reflex responses in cats. The present experiments were performed to determine whether CSA activated by epicardial bradykinin also mediate solely excitatory reflex responses in the dog. The changes in efferent cardiac or renal sympathetic nerve activity, mean arterial pressure, and heart rate resulting from application of bradykinin to the left ventricular epicardial surface were determined in 15 chloralose-anesthetized, sinoaortic-denervated vagotomized dogs. Activation of CSA with bradykinin (0.1--120 g/ml) elicited inhibitory responses in eight dogs, excitatory responses in four dogs, and biphasic responses in three dogs. Both excitatory and inhibitory reflexes were eliminated by cardiac sympathetic afferent denervation. The results show that, in the dog, cardiac receptors with sympathetic afferent fibers activated by epicardial bradykinin mediate nonuniform reflex responses that tend to be predominantly inhibitory.

Cardiovascular and sympathetic responses reflexly elicited through the excitation with bradykinin of sympathetic and vagal cardiac sensory endings in the cat.

The intracoronary administration of bradykinin (30 ng·kg−1) was used to study the reflex responses to the excitation of sympathetic and vagal cardiac sensory endings in anaesthetised cats. The left main coronary artery was perfused with a constant flow pump to administer the drug without concomitant manipulations of the heart. The reflex effects were assessed by recording simultaneously target haemodynamic functions and the impulse activity of sympathetic preganglionic fibres, isolated from an outflow largely directed to the heart. In eight out of 13 cats with intact cardiovascular innervation the intracoronary injection of bradykinin produced a consistent and significant increase in systemic mean arterial pressure (MAP), left ventricular pressure (LVP) and LVdP/dtmax along with a significant increase in the sympathetic efferent impulse activity. In the remaining five animals, bradykinin caused a significant haemodynamic depressor response concomitant with a slight increase in sympathetic impulse activity. In eight additional cats with sinoaortic denervation, excitatory or inhibitory haemodynamic reflex responses were also observed, the types of response being consistent in each individual animal. However, in the case of inhibitory responses the sympathetic impulse activity was simultaneously decreased. After vagotomy, bradykinin induced a significant increase in MAP, LVP, LVdP/dtmax and in cardiac sympathetic efferent activity in all 21 cats. These excitatory responses were abolished after the interruption of a large part of the cardiac sympathetic afferents. Thus the intracoronary administration of bradykinin induced haemodynamic and sympathetic reflex responses that were dependent upon the interaction of opposite influences mediated by the simultaneous activation of cardiac vagal and sympathetic afferents.

Excitation of cardiac sympathetic afferent nerves: effects on renal function.

Cardiac sympathetic afferent nerves can reflexly alter renal efferent nerve activity during myocardial ischemia and in response to mechanical or chemical stimulation of cardiac receptors. They also may influence renal excretion of water and electrolytes; however, this potential influence on renal function has not been determined. Therefore, receptors of cardiac sympathetic afferent nerves were chemically stimulated by epicardial application of bradykinin to determine effects on renal function. Experiments were performed in anesthetized dogs in which cervical vagosympathetic trunks were severed and common carotid arteries were tied to diminish influences of arterial baroreceptors and vagal afferent nerves. Chemical stimulation of cardiac afferent neurons excited renal nerve activity and produced decreases in urine flow rate, glomerular filtration rate, and excretion of sodium and potassium. In contrast, no consistent changes in renal function were observed in control dogs, which did not undergo cardiac afferent stimulation. These data provide evidence that activation of cardiac sympathetic afferent neurons can lead to alterations in excretion of water and electrolytes as well as changes in renal nerve activity.

Contrasting reflex influences of cardiac afferent nerves during coronary occlusion.

Afferent neurons contained within cardiac sympathetic nerves may have important influences on the circulation when activated during myocardial ischemia. Although such activation is known to reflexly excite upper thoracic sympathetic efferent neurons, effects on other components of sympathetic outflow are unknown. Therefore, cardiac sympathetic afferent nerves were stimulated by occlusion of coronary arteries to investigate their reflex influences on renal sympathetic nerve activity and systemic arterial blood pressure. Responses were observed in anesthetized cats in which sympathetic and/or vagal cardiac afferent nerves remained intact and arterial baroreceptors remained intact or had been denervated. Stimulating sympathetic afferent neurons caused excitation of renal nerve activity, which was accompanied by variable changes in arterial pressure. Stimulation of vagal afferents by coronary occlusion consistently produced inhibition of renal nerve activity and marked depressor responses. When both components of cardiac innervation remained intact, increases or decreases in renal nerve activity and blood pressure were elicited by coronary artery occlusion in the presence or absence of arterial baroreceptors. These results illustrate that cardiac sympathetic afferent nerves can contribute significantly to cardiovascular control during myocardial ischemia.

Excitation of afferent cardiac sympathetic nerves is modulated by nitroglycerin.

AbstractWe examined the effect of nitroglycerin on stimulation of sympathetic nerve fibers arising from receptor sites in the left ventricular wall during acute coronary artery occlusion. Sympathetic afferent nerve activity was recorded in single and multifiber nerve preparations dissected from slips of T3 white rami communicantes. Acute left anterior descending or left circumflex coronary artery occlusion produced an increase in segmental myocardial length and excitation of afferent cardiac sympathetic nerve fibers in the region of the myocardium supplied by the occluded artery. Intravenous administration of nitroglycerin in doses up to 100 μg/kg and sodium nitroprusside (50 μg/min) reduced systolic bulge during coronary occlusions and suppressed excitation of these myelinated and unmyelinated afferent fibers. Local intracoronary injection of nitroglycerin (100 μg) produced neither a change in systemic blood pressure nor a change in excitation of the afferent nerve fibers during coronary occlusion. Syste...

Reversible blockade of myelinated and non-myelinated cardiac afferents in cats by instillation of procaine into the pericardium.

Pericardial local anaesthesia was instituted in 33 chloralosed cats through catheters implanted into the pericardium. The activity of 1531 single fibres teased from either vagus in the neck was identified and classified according to source. Random testing with 2% procaine instilled into the pericardium revealed that only cardiac afferents could be blocked. Arterial and other receptors were unaffected. Blocking concentrations were determined for 38 non-myelinated cardiac afferents (mean conduction velocity 1.3 m.s-1) and for 43 myelinated fibres (mean conduction velocity 19 m.s-1). Blocking concentrations varied widely but equally for both fibre categories between 0.05% and 2.0% procaine. Non-myelinated fibres required a mean concentration of 0.26% procaine for block, whereas myelinated fibres needed a mean concentration of 0.45% (P less than 0.01). The large overlap in the frequency distributions of the blocking concentrations for both sets of fibres, would not, however, allow the blocking of one fibre category without affecting the other. Additionally two cardiac sympathetic afferents were blocked at 0.25 and 0.5% procaine. Mean times for block onset and recovery for non-myelinated fibres were 3.05/1.98 min and for myelinated fibres 1.4/0.59 min, respectively. Pericardial local anaesthesia is selective for cardiac afferents but does not allow for differential block of a given fibre category. A 1% solution of procaine will eliminate the heart as a reflexogenic area.

Contrasting reflexes evoked by chemical activation of cardiac afferent nerves.

Afferent neurons within cardiac sympathetic nerves can reflexly excite central sympathetic outflow. However, their contribution to cardiovascular control remains unclear because they are potentially opposed by inhibitory reflexes of cardiac vagal or arterial baroreceptor afferent origin. It was considered that sympathetically mediated, excitatory responses might be more prominent when initiated by chemical stimulation. In chloralose-anesthetized, vagotomized, sinoaortic-denervated cats, epicardial or intracoronary administration of bradykinin or potassium chloride evoked renal nerve excitation and pressor responses mediated by cardiac sympathetic afferent nerves. When upper thoracic sympathetic nerves were severed, and vagal afferent nerves remained intact, bradykinin and potassium chloride produced inhibition of renal nerve activity and depressor responses. When sympathetic and vagal components of cardiac innervation remained intact, these substances produced excitation, inhibition, or no change in sympathetic outflow. Excitation occurred as often as inhibition. A similar pattern was observed when arterial baroreceptor nerves remained intact. These data illustrate that cardiac sympathetic afferent neurons can have significant excitatory influences on the cardiovascular system in spite of opposition by inhibitory afferent groups.

Coronary pressor reflexes

The heart differs from other cardiovascular reflexogenic structures because it has two prominent inputs to the central nervous system. One input is spinal and is mediated by afferent cardiac sympathetic nerve fibers. The other is medullary and is mediated by afferent vagal fibers. The number of fibers projecting centrally appears to be similar in the two systems. The reflex effects produced by excitation of the two inputs are complicated and can be either pressor or depressor. However, reflex pressor effects seem to be more prominent for the spinal input and reflex depressor effects more prominent for the medullary input.

Afferent sympathetic unmyelinated fibres with left ventricular endings in cats.

1. We recorded the electrical impulse activity of thirty-three single afferent fibres with left ventricular endings from the third and fourth left thoracic sympathetic rami communicantes of anaesthetized cats. Their conduction velocity ranged from 0.23 to 0.98 m/sec (group C). 2. The endings of each fibre were localized to the left ventricle by mechanical probing performed at the end of the experiment on the non-beating heart. No fibre had multiple sensory fields. 3. The impulse activity (0.95 +/- 0.2 impulses/sec) was spontaneous but most often a fixed temporal correlation between impulses and ventricular dynamics was not detectable. It was increased during occlusion of the thoracic aorta, I.V. administration of isoprenaline or infusion of saline. It was unaffected by asphyxia, haemorrhage and I.V. administration of acetylcholine. It was decreased during occlusion of inferior vena cava. Therefore these ventricular receptors appeared to be mainly sensitive to mechanical events. 4. The fibres were excited during the occlusion of the left main coronary artery, after a latency of 14.5 +/- 1.3 sec. They were also excited during ventricular fibrillation, exhibiting the highest values of impulse activity (2.51 +/- 0.4 impulses/sec). The increase in impulse activity during ventricular fibrillation was sometimes immediate and extreme, with peak frequencies of about 50 impulses/sec. 5. These spontaneously active ventricular receptors with unmyelinated nerve fibres participate in the transmission of the continuous impulse activity which from the cardiovascular system reaches the spinal cord through the sympathetic nerves and which is likely to contribute to the neural control of circulation. Thus the unmyelinated cardiac sympathetic afferents should not be considered as purely nociceptive in function.

Avian sympathetic cardiac fibers and their cells of origin: anatomical and electrophysiological characteristics

The sympathetic cardiac innervation of the pigeon was investigated to describe certain anatomical and physiological properties of the cardiac nerve fibers and their postganglionic cells of origin. The compound action potential of the right cardiac nerve has two major components, one conducting at 2.0–5.6 m/sec with no chronotropic effect on the heart and the other conducting at 0.4–2.0 m/sec with a cardioacceleratory effect. Postganglionic neurons responding antidromically to cardiac nerve stimulation were then studied in ganglion 14 which contains most cells of origin of the cardiac fibers. These neurons have refractory periods of approximately 4 msec, following frequencies of < 4Hz, and axons conducting at 0.4–2.0 m/sec; this conduction velocity range corresponds to the slower compound action potential component. Electron microscopy of the cardiac nerve revealed unmyelinated fibers ranging in diameter from 0.2 to 1.2 μm and a population of myelinated fibers 1.0–3.6 μm in diameter. The unmyelinated fibers account for the slower compound action potential component and are largely postganglionic cardioaccelerator axons. The myelinated fibers account for the faster compound action potential component which has no chronotropic effect and is not reflected in postganglionic antidromic latencies; it is suggested that these myelinated fibers are cardiac sympathetic afferents. This study thus establishes electrophysiological criteria for identifying cardiac postganglionic neurons and describes the anatomical basis of these criteria.

Autonomic afferents at T1 in elicitation of volume-induced tachycardia in the dog.

Intravenous infusion of blood elicited tachycardia in anesthetized dogs with beta-receptor blockade (dogs with vagal efferents intact but cardiac sympathetic efferents blocked) and bradycardia in dogs with combined beta-receptor blockade and rhizotomy at T1 (dogs with vagal efferents intact but cardiac sympathetic efferents plus autonomic afferents at T1 blocked). This suggests that tachycardia elicited by volume in infusion may be partly due to a reflex with its afferent pathway at the T1 segment of the spinal cord and its efferent pathway in the vagi. Moreover, infusion evoked bradycardia in dogs with right-sided rhizotomy at T1, which was not significantly different from the response elicited in dogs with bilateral rhizotomy at T1. Additionally, the tachycardia response induced in dogs with ventral or dorsal rhizotomy at T1 was significantly different from the bradycardia response elicited in dogs with both dorsal and ventral rhizotomy at T1. These results suggest that the afferent pathway predominates on the right side, and its entry at T1 may be via both dorsal and ventral roots.

Response of left ventricular mechanoreceptors to changes in pressure and muscle length.

SummaryWe conclude that the increase in isovolumetrically developed intraventric-ular pressure is associated with an enhanced activity of cardiac sympathetic afferents traversing the left upper thoracic white rami communicantes, as reported by Hess et al. (8). Moreover, the sympathetic afferent nerve fibers respond to alteration in myocardial muscle length occurring in isobaric diastole and thus respond to a displacement stimulus as well as to a pressure stimulus.

Activation of afferent cardiac sympathetic nerve fibers of the cat by pain producing substances and by noxious heat.

Afferent discharges of 64 single units were recorded from the left cardiac sympathetic nerve of anesthetized cats. Mechano-sensitive terminals of the afferent fibers were localized in the extrapulmonary part of the pulmonary artery, left atrium, left ventricle and left pericardium, as determined by direct mechanical probing of the heart after death of the animals. Conduction velocity of the fibers ranged from 2.5 to 14.6 m/s. Excitation of these Adelta-fibers with mechanically excitable endings was produced by intravenous injections of acetylcholine, 5-hydroxytryptamine, bradykinin, histamine and veratridine, and/or by topical application of these agents to the receptor region. Noxious heat to the mechanically excitable field in the wall of the pulmonary artery and the left ventricle also activated their afferent fibers. These observations provide evidence for a certain number of afferent units in the cardiac sympathetic nerve with polymodal sensitivity. These afferent fibers can provide the spinal cord with information not only on mechanical changes in cardiac events, but also changes in the chemical environment of the cardiac nerve ending, possibly produced by myocardial ischemia.

Cyclical reduction in blood flow of partially constricted coronary artery in dogs. II. An arteriographic study.

Mechanisms for cyclical reduction in peripheral blood pressure and flow of partially constricted coronary artery of anesthetized dogs has been examined. In 64 of 97 preparations, cyclical reduction in coronary blood pressure and flow developed 3 to 32 min after the beginning of constriction. Period duration of the cyclical reduction ranged from 1 to 32 min. The cyclical reduction was frequently associated with elevation of the ST segment of surface electrocardiogram, systolic bulge of the left ventricle and excitation of afferent cardiac sympathetic nerve fibers. In the preparations in which cyclical reduction was not produced by constriction, a brief stretching of the constricted portion provoked the cyclical reduction. Segmental or diffuse narrowing of the constricted coronary artery which occurred during the reduction in pressure and flow was demonstrated by selective arteriography. Also, segmental spasm in the constricted coronary artery was demonstrated by photography. No obvious difference in the constricted of the artery was observed histologically between the preparations in which cyclical reduction developed and those in which cyclical reduction was not produced. The results indicate participation of vasospasm in the cyclical reduction of blood pressure and flow in partially constricted coronary artery.