Thoracic Cardiac Nerves Research Articles

Human adult cardiac autonomic innervation: Controversies in anatomical knowledge and relevance for cardiac neuromodulation.

Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These treatments require detailed knowledge of the spatial location and distribution of cardiac autonomic nerves, however, there are controversies on this subject in humans. To provide a systematic overview of current knowledge on human anatomy of the cardiac autonomic nervous system. In contrast to the often claimed assumption that human preganglionic sympathetic cardiac neurons originate mainly from thoracic spinal segments T1-T4 or T5, there is ample evidence indicating involvement of cervical spinal segment C8 and thoracic spinal segments below T5. Whether cervical ganglia besides the stellate ganglion play a role in transmission of cardiac sympathetic signals is unclear. Similarly, there is debate on the origin of cardiac nerves from different thoracic ganglia. Most human studies report thoracic cardiac nerves emerging from the first to fourth thoracic paravertebral ganglia; others report contributions from the fifth, sixth and even the seventh thoracic ganglia. There is no agreement on the precise composition of nerve plexuses at the cardiac level. After years of debate, it is generally accepted that the vagal nerve contributes to ventricular innervation. Vagal distribution appears higher in atria, whereas adrenergic fibers exceed the number of vagal fibers in the ventricles. Anatomy of the human cardiac autonomic nervous system is highly variable and likely extends beyond generally assumed boundaries. This information is relevant for thoracic epidural anesthesia and procedures targeting neuronal modulation of cardiac sympathetic innervation.

Topological changes of the human autonomic cardiac nervous system in individuals with a retroesophageal right subclavian artery: two case reports and a brief review

The topological changes of the human autonomic cardiac nervous system in two cadavers with a retroesophageal right subclavian artery (Rersa) were compared with the normal autonomic cardiac nervous system. The following new results were obtained in addition to the conventional deficient finding of the right recurrent laryngeal nerve. (1) Right superior cardiac nerves arising from the superior cervical ganglion were consistently observed in both cadavers, in addition to the right thoracic cardiac nerves along the Rersa. (2) A segmental accompanying tendency of the right cardiac nerves was recognized: the cardiac nerves arising from the sympathetic trunk cranial to the middle cervical ganglia ran along with the right common carotid artery, whereas the cardiac nerves arising from the sympathetic trunk caudal to the vertebral ganglion ran along the Rersa. (3) The right thoracic cardiac nerves, which have never been observed to accompany the normal right subclavian artery, ran along the proximal part of the Rersa. According to previous reports of individuals with the Rersa, a thick right thoracic cardiac nerve is commonly observed instead of a right superior cardiac nerve. However, all the cardiac nerves were recognized in both the individuals described in the present report. Therefore, we strongly disagree with the previous idea that the origin of the right cardiac nerves from the sympathetic trunk and ganglia is shifted caudally in individuals with the Rersa. The topological changes of the autonomic cardiac nervous system in two cases of Rersa also reflected spatial changes of great arteries.

Extrinsic Cardiac Nerve Distribution in Goitred Gazelle (Gazella subgutturosa)

Extrinsic cardiac nerves and their patterns are described based on anatomical dissections of five goitred gazelle. Sympathetic cardiac innervation was mainly provided by the cervicothoracic and thoracic cardiac nerves. No left caudal cervicothoracic nerves, middle cervical cardiac nerves and vertebral cardiac nerves from the vertebral ganglion were observed. Parasympathetic cardiac innervation was supplied by the nerve fibres from the caudal vagal cardiac rami only. No cardiac rami from the cranial vagal cardiac nerves present in small ruminants were observed in this study. The caudal laryngeal and phrenic cardiac nerves also contributed to the cardiac innervation.

Comparative anatomical study of the autonomic cardiac nervous system in macaque monkeys

The main aim of this study was to clarify the general morphology of the autonomic cardiac nervous system in macaque monkeys. A submacroscopic comparative anatomical study of the autonomic cardiac nervous system was performed by examining 22 sides of 11 bodies of four species of macaque monkeys, including some previously unreported species (pig-tailed and stump-tailed monkeys), under a surgical stereomicroscope. The following results were obtained. 1) The basic arrangement of the autonomic cardiac nervous system is constant in all examined macaques. 2) A superior cardiac nerve originating from the superior cervical ganglion was not observed, whereas the thoracic cardiac nerve originating from the sympathetic trunk/ganglia under the cervicothoracic ganglion was rarely observed in all the examined macaques. 3) The main cardiac nerve is the middle cardiac nerve originating from the middle cervical ganglion, similar to the situation in humans. 4) Although the superior, inferior, and thoracic cardiac branches of the vagus nerve were consistently observed, the left thoracic cardiac branch is rarely absent because of its lower origin to the heart. 5) The cranial autonomic nerves tend to distribute into the heart medially (arterial porta), and the caudal autonomic nerves tend to distribute into the heart laterally (venous porta). To comprehend the comparative morphological and evolutionary changes more completely, these results were compared with our previous studies and some references. Consequently, differences in the sympathetic cardiac nerves of macaques and humans are recognized, in spite of the similar morphologies of the vagal cardiac branches. These differences include the composition of the cervicothoracic ganglion, the lower positions of the middle cervical and cervicothoracic ganglia, and the narrow range for the origin of the cardiac nerves in macaques compared to that in humans.

The autonomic nervous system of the human heart with special reference to its origin, course, and peripheral distribution

A submacroscopic anatomical investigation of the entire autonomic cardiac nervous system, from origin to peripheral distribution, was performed by examining 36 sides of 18 adult human cadavers under a stereomicroscope. The following new results and points of discussion were obtained: (1) The superior cervical, the middle cervical, the vertebral, and the cervicothoracic (stellate) ganglia, composed of the inferior cervical and 1st thoracic ganglia, were mostly consistent among the specimens. (2) The superior, middle, and inferior cardiac nerves innervated the heart by simply following the descent of the great arteries. In contrast, the thoracic cardiac nerve in the posterior mediastinum followed a complex course because of the long distance to the middle mediastinum. (3) The actual course of the right thoracic cardiac nerve differed from that of the previous descriptions in that it ascended obliquely or ran transversely to the vertebrae, regardless of the intercostal vessels. Regarding the right thoracic cardiac nerve, two descending courses were observed: the descent of the right thoracic cardiac nerve via the azygos vein and right venous porta, and the descent of the recurrent right thoracic cardiac nerve via the aorta. (4) The cranial cardiac nerve and branch tended to distribute into the heart medially, and the caudal cardiac nerve and branch tended to distribute into the heart laterally. (5) The mixing positions (cardiac plexus) of the sympathetic cardiac nerve and the vagal cardiac branch, as well as the definitive morphology of brachial arteries with the recurrent laryngeal nerves, tended to differ on both sides. These new and detailed anatomical descriptions of the human autonomic cardiac nervous system may provide important clues regarding the morphogenesis of autonomic cardiac nerves in addition to contributing to the improvement of cardiac surgery.

Increased cardiac sympathetic nerve activity following acute myocardial infarction in a sheep model

The time course of cardiac sympathetic nerve activity (CSNA) following acute myocardial infarction (MI) is unknown. We therefore undertook serial direct recordings of CSNA, arterial blood pressure (MAP) and heart rate (HR) in 11 conscious sheep before and after MI, and compared them with 10 controls. Conscious CSNA recordings were taken daily from electrodes glued into the thoracic cardiac nerves. Infarction was induced under pethidine and diazepam analgesia by applying tension to a coronary suture. MI size was assessed by left ventricular planimetry (%) at postmortem, peak troponin T and brain natriuretic peptide levels (BNP). Baroreflex slopes were assessed daily using phenylephrine-nitroprusside ramps. The mean infarcted area was 14.4 +/- 2.9%, troponin T 1.88 +/- 0.39 microg l(-1) and BNP 8.4 +/- 1.3 pmol l(-1). There were no differences in haemodynamic parameters or CSNA between groups at baseline. MAP and HR remained constant following MI. CSNA burst frequency increased from baseline levels of 55.8 +/- 7.1 bursts min(-1) to levels of 77.5 +/- 8.7 bursts min(-1) at 2 h post-MI, and remained elevated for 2 days (P < 0.001). CSNA burst area also increased and was sustained for 7 days following MI (P= 0.016). Baroreflex slopes for pulse interval and CSNA did not change. CSNA increases within 1 h of the onset of MI and is sustained for at least 7 days. The duration of this response may be longer because the recording fields decrease with time. This result is consistent with a sustained cardiac excitatory sympathetic reflex.

Continual recordings of cardiac sympathetic nerve activity in conscious sheep.

Cardiac sympathetic nerve activity (CSNA) is of major importance in the etiology of heart disease but is impossible to measure directly in humans. Ovine and human cardiovascular systems are similar; therefore, we have developed a method for the daily recording of CSNA in conscious sheep. After thoracotomy, electrodes were glued into the left thoracic cardiac nerve and CSNA, blood pressure (BP), and heart rate were recorded daily. Satisfactory recordings > or =7 days of CSNA were obtained in 11 of 28 sheep (40%), mean recording time 10.6 days, range 7-47. During the first week, CSNA decreased gradually from 78 +/- 8 at baseline to 60 +/- 7 bursts/min on day 5 (P = 0.02) or from 76 +/- 9 to 57 +/- 7 bursts/100 beats on day 7 (P = 0.04). Similarly, BP decreased from 103 +/- 4 to 94 +/- 4 mmHg (P = 0.03). Low-frequency heart rate variability decreased from 0.12 +/- 0.02 to 0.06 +/- 0.02 ms(2) on day 6 (P = 0.004) but was not correlated to CSNA. In conclusion, CSNA that can be continually recorded in conscious sheep decreases during the first week postsurgery and, thereafter, stabilizes. This model should provide valuable insights in future investigations of cardiac disease.

Attenuation of baroreflex changes in cardiac sympathetic efferent activities during acute myocardial ischemia

Sympathetic efferent activities to the heart during blood pressure changes were investigated in 11 dogs with acute myocardial ischemia. Normalized sympathetic efferent activities recorded in thoracic cardiac nerves decreased or increased as anticipated in response to transient changes in mean arterial pressure (15 to 25 mm Hg with nitroglycerin or phenylephrine, 2 to 8 μg/kg, intravenously). A branch of the left circumflex coronary artery was occluded, and the arterial pressure challenges were repeated at 5, 15, and 25 minutes after the occlusion. The control (preocclusion) responses in sympathetic efferent activities to the heart ranged from ±2% to 70% (changes relative to steady state normalized at 100%). Reflex sympathetic efferent responses were diminished at 15 and 25 minutes of ischemia. Several sympathetic efferent baroreflex responses during myocardial ischemia were paradoxic. Reflex sympathetic efferent changes were not affected in sham animals. These results indicate that both increases and decreases in cardiac sympathetic efferent activities during baroreflex challenges are attenuated within 15 to 25 minutes of acute coronary artery occlusion. These findings suggest that an abnormal buffering of blood pressure changes during acute myocardial ischemia might lead to autonomic dysfunction that promotes arrhythmogenesis and sudden cardiac death.

Effect of cardiac denervation on cardiorespiratory responses to exercise in goats

The purpose of this study was to determine whether intact cardiac innervation and a normal cardiovascular (CV) response are required for a normal ventilatory (VE) response to mild and moderate treadmill exercise in awake goats. Accordingly, we measured CV and respiratory responses to two levels of exercise in seven normal (N) and six cardiac-denervated (CD) goats. Evidence of surgical CD included 1) absence of a cardiac response during surgery when the left thoracic cardiac nerves, thoracic vagi, and right and left stellate ganglia were electrically stimulated, 2) total and 80% attenuation of baroreflex changes in heart rate (HR) when arterial blood pressure was raised or lowered, respectively, by infusion of vasoactive agents in awake goats, and 3) attenuation of the CV responses to exercise. At each level of exercise in the CD goats, the HR response was significantly reduced relative to the response observed before CD (P less than 0.05) and the recovery HR response was delayed. Cardiac index increased in a work rate-dependent manner in N and CD goats but was significantly lower in the CD animals (P less than 0.05). Hypotension was consistently observed during exercise following CD. There was no effect of CD on steady-state VE at any metabolic rate or on the VE-O2 uptake relationship (P greater than 0.05). The rest-to-work and work-to-work transition responses of arterial PCO2 were similar between N and CD goats, but there was a tendency toward greater hypocapnia at the exercise onset in CD goats at the highest work rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential cardiac sympathetic activity during acute myocardial ischemia

Efferent sympathetic activities were simultaneously recorded from two thoracic cardiac nerves in 33 chloralose-anesthetized dogs. Efferent innervation patterns were determined by electrical stimulation prior to recording in each animal. One of the nerves selected for recording was shown to innervate the proposed ischemic region, whereas the other nerve was selected because it was shown to innervate nonischemic regions. Left ventricular ischemia was produced by occlusion of a branch of either the left anterior descending (LAD) or left circumflex (LCX) coronary arteries. Heart rate was paced. Cardiac postganglionic sympathetic efferent activities were recorded during a 30-min coronary occlusion in 22 animals. Thirty minutes after LAD occlusion (n = 10), postganglionic sympathetic activity to ischemic myocardium was decreased (84 +/- 5% of control; P less than 0.05) while activity to nonischemic myocardium was unchanged. Thirty minutes after LCX occlusion (n = 12), postganglionic sympathetic activity to ischemic myocardium was also decreased (87 +/- 3% of control; P less than 0.01); however, sympathetic activity to nonischemic myocardium was increased (159 +/- 10% of control; P less than 0.001). Thus, in the anesthetized canine, regional left ventricular ischemia elicits differential sympathetic neural responses that are dependent on the location of the ischemic myocardium as well as the efferent destinations of the nerves. Changes in cardiac postganglionic sympathetic efferent activities are characterized by decreased activity to ischemic regions, with either no change or increased activity to nonischemic regions.

Baroreflex modulation of heart rate and initiation of atrial activation in dogs.

In open-chest dogs, blood pressure was regulated by titrating doses of phenylephrine and nitroprusside to determine its effect on heart rate and pacemaker location. Changes in blood pressure correlated with changes in heart rate (r = 0.86). Activation time mapping demonstrated multicentric atrial activation, with a site of origin-rate relationship. The fastest pacemakers were located in the most cranial regions and slowest in the most caudal areas. In this chloralose-morphine anesthetized model, autonomic blockade with atropine and propranolol suggests that acute baroreflex-induced changes in heart rate were mediated exclusively by either increased sympathetic or parasympathetic tone and were not associated with inhibition of the opposite system. Division of right and left thoracic cardiac nerves indicated the left sympathetics participated in the baroreflex in 50% of the animals and the left parasympathetics in 90% of the animals. Both the right sympathetics and parasympathetics were active in the baroreflex in all animals. The data demonstrate that physiological heart rate response is regulated through an extensive system of right atrial pacemakers modulated by both left and right efferent cardiac nerves.

Influence of atrial mechanoreceptors upon the sympathetic efferent activity elicited during a cardiogenic chemoreflex in the dog

Two different cardiogenic reflexes were studied for their effects upon the activity recorded from the thoracic cardiac nerves of 7 chloralose-anesthetized dogs. Sympathetic efferent activity in 5 right and 7 left anterior ansa multifiber preparations was quantitatively analyzed. A cardiogenic hypertensive chemoreflex was induced by administration of serotonin (100 μg/ml, 2 ml) into the left atrium before, during and after inflation of balloons in the right and/or left atrial appendages. Balloon inflations alone resulted in heart rate increases of 5–20 bpm but arterial blood pressure, pulse pressure and end diastolic pressure were not significantly affected. Control serotonin-induced efferent discharges were 174 ± 10% (mean ± S.E.M.) of resting activity with a duration of 5.2 ± 0.4 s. During inflation of both atrial balloons, the serotonin-induced efferent discharges were 165 ± 14% (N.S.) of resting activity with a duration of 7.8 ± 0.7 s ( P < 0.011). Following release of the balloons, the serotonin-induced discharges were 152 ± 17% (N.S.) of resting activity with a duration of 4.9 ± 0.4 s (N.S.). These results suggest that afferent signals from atrial mechanoreceptors can act to increase the duration but not the total intensity of the efferent sympathetic discharges elicited during a cardiogenic chemoreflex.

Responses of the canine myocardium to stimulation of thoracic cardiac nerves.

The thoracic cardiac nerves were stimulated in each of 21 dogs anesthetized with alpha chloralose. Recordings were made of heart rate, blood pressure, and contractile force from all four cardiac chambers. Walton-Brodie strain-gauge arches were sutured to both atria, and to three locations of each ventricle, representing both anterior and posterior surfaces. The functional autonomic components of each nerve were summarized and classified into four basic types. Types I and II were both located medial to the thoracic vagi. These were shown to contain both sympathetic and parasympathetic components traveling to all four chambers of the heart. The sympathetic componnent of the type II nerves produced reflex changes in force of contraction and systemic blood pressure. Nerves classified as types III and IV produced no parasympathetic effect on the heart. These were all located lateral to the thoracic vagi. While the type III nerves carried sympathetic efferent fibers to all four chambers, the type IV nerve carried sympathetic fibers predominantly to the right atrium.

Intra-SA-nodal pacemaker shifts induced by autonomic nerve stimulation in the dog.

Pacemaker shifts in the canine heart were inferred during stimulation of thoracic cardiac nerves and following norepinephrine from changes in the initial site of activation of bipolar electrodes sutured over the rostral, middle, and caudal regions of the sinus node, over the internodal pathways, and His bundle. During control periods, pacemaker activity was localized within the sinoatrial (SA) node 87% of the time, with the middle electrode most frequently showing initial activation. Stimulation of the right-sympathetic nerves enhanced sinus node pacemaker dominance, shifting it rostrally within the node. Right-vagal stimulation shifted the pacemaker caudally within the SA node, to nonnodal sites, and to the lower atrioventricular node and His bundle. Left-sympathetic stimulation shifted the pacemaker caudally within the sinus node and enhanced pacemaker activity in the vicinity of the internodal pathway electrodes and His bundle. Dispersion of pacemaker activity was particularly apparent during stimulation of the ventrolateral cervical cardiac nerve. Stimulation of the left-vagal nerves produced effects similar to those of the left-sympathetic nerves. Norepinephrine enhanced pacemaker activity particularly in the rostral region of the sinus node. Slight shifts in pacemaker activity within the sinus node produced changes in pattern of atrial excitation.

Cardiac pain: anatomic pathways and physiologic mechanisms.

It may be concluded that the pathways of cardiac pain have been thoroughly established, with the exception of the conduction of anginal attacks occasionally referred to the neck and jaws. Afferent impulses traverse axons that travel in the cervical and thoracic sympathetic cardiac nerves. In the case of the cervical pathway, all impulses on entering the paravertebral ganglionated chain in the neck must descend to the upper thoracic level before they can gain access to the spinal cord. Other impulses reach the 3 superior thoracic ganglia via the more direct thoracic cardiac nerves. Both the cervical and thoracic fibers join the spinal nerves over the communicant sympathetic rami. After passing through the intervertebral foramina, they enter the posterior roots and terminate in the lateral horn of the spinal cord. Here they establish synapses with secondary afferent neurons of the spinothalamic tract, decussate to the opposite anterior column, and are carried rostrally to the nucleus ventralis posterolateralis of the thalamus. This is the principal locus in the brain for the perception of visceral pain. In contrast to well-defined cutaneous sensibility, there is no cortical area for exact visceral localization in the postcentral region of the cerebral cortex. Another factor in the poor localization of cardiac pain is the paucity of sensory endings in the heart. A third appears to be the limited number of secondary sensory fibers in the spinothalamic tracts. These central axons must be shared with other impulses from the surface of the body. As a result, pain from the heart is in large part referred to the cutaneous distribution of the upper 4 thoracic spinal segments. Accounting for the superficial reference of visceral pain by Mackenzie's theory of a viscerocutaneous reflex is no longer justifiable. Even after cutaneous afferent fibers are interrupted by procaine or amputation of the arm, pain from the heart can still be felt over its previous distribution. Neither stimulation of the vagi nor interruption of transmission in these nerves has been found to have any beneficial effect in patients suffering from angina pectoris. Sensory denervation of the heart must therefore be carried out by destruction of the upper ganglia in the thoracic sympathetic trunks or by severing the corresponding posterior spinal roots.