Cervical Spinal Cord Transection Research Articles

Complete cervical spinal cord transection cephalad to noncontiguous sub-axial vertical distraction injury: a rare complex injury case report, surgical technique and literature review

Complete cervical spinal cord transection cephalad to noncontiguous sub-axial vertical distraction injury: a rare complex injury case report, surgical technique and literature review

The Left-Right Side-Specific Neuroendocrine Signaling from Injured Brain: An Organizational Principle.

A neurological dogma is that the contralateral effects of brain injury are set through crossed descending neural tracts. We have recently identified a novel topographic neuroendocrine system (T-NES) that operates via a humoral pathway and mediates the left-right side-specific effects of unilateral brain lesions. In rats with completely transected thoracic spinal cords, unilateral injury to the sensorimotor cortex produced contralateral hindlimb flexion, a proxy for neurological deficit. Here, we investigated in acute experiments whether T-NES consists of left and right counterparts and whether they differ in neural and molecular mechanisms. We demonstrated that left- and right-sided hormonal signaling is differentially blocked by the δ-, κ- and µ-opioid antagonists. Left and right neurohormonal signaling differed in targeting the afferent spinal mechanisms. Bilateral deafferentation of the lumbar spinal cord abolished the hormone-mediated effects of the left-brain injury but not the right-sided lesion. The sympathetic nervous system was ruled out as a brain-to-spinal cord-signaling pathway since hindlimb responses were induced in rats with cervical spinal cord transections that were rostral to the preganglionic sympathetic neurons. Analysis of gene-gene co-expression patterns identified the left- and right-side-specific gene co-expression networks that were coordinated via the humoral pathway across the hypothalamus and lumbar spinal cord. The coordination was ipsilateral and disrupted by brain injury. These findings suggest that T-NES is bipartite and that its left and right counterparts contribute to contralateral neurological deficits through distinct neural mechanisms, and may enable ipsilateral regulation of molecular and neural processes across distant neural areas along the neuraxis.

Cervical Spinal Cord Transection (SCT) Increases Gastric Compliance in Anesthetized Rats

Abstract Spinal cord injury (SCI) can markedly alter the autonomic nervous system’s functions. It immediately causes autonomic and somatic hypo- or arreflexia, a state known as spinal shock. SCI determines the enhancement of two gastric reflexes that appear in normal conditions: the receptive and adaptative reflexes. Furthermore, this study also tried to evaluate the causes that led to such modifications: either vagal control, nitric oxide (NO)-pathways or intestine-intestinal reflexes. Male Wistar rats (N=25) were subjected to laminectomy (Sham group) or laminectomy + complete Spinal Cord Transection (SCT), between C7 and T1 vertebrae under anesthesia (SCT group). Before the surgery, the rats had water and food ad libitum; after the surgery, rats were fasted for 24 hours, still having access to water. The next day, all animals were subjected to a catheterism of their right carotid artery, a tracheostomy and a flexible balloon introduction down to the stomach’s fundix region, also under anesthesia. Rats were connected to a Power-Lab® system, via a pressure transducer (in order to measure the arterial pressure – MAP - and the heart rate - HR), and to a modified Plethysmometer (in order to measure the fundical gastric volume - GV variation). Vagal control was studied via cervical vagotomy; NO-mediation - via NO synthesis inhibitors (L-NAME); intestinointestinal reflexes - by using laxatives (Lactulone). Statistical analysis revealed, in some cases, that GV is significantly (p<0.05) augmented in SCT rats (2,4±0,09; 3,1±0,05; 3,7±0,06 ml) than in Sham (2,2±0,12; 2,9±0,12; 3,3±0,15 ml). Nevertheless, MAP and HR, were subsequently lower (p<0.05) in SCT (63,5±21,1mm Hg; 227,1±25,2 BPM) than in the control group (88,2±14,4mm Hg; 427,0±19,2 BPM). In summary, the increase of GV in SCT, seems to involve vagal pathways and/or NO-mediation, but still not neglecting the colic-gastric reflexes.

Traumatic cervical spinal cord transection.

MRI plays a crucial role in the assessment of spinal cord injury in cervical trauma. Transection of the cord is a rare post-traumatic cord injury, which appears on T 2W images as a high signal between the two disrupted ends of the cord.

Physical and electrical characterization of TexasPEG: An electrically conductive neuronal scaffold.

Background:Graphene and its derivatives have been shown to be biocompatible and electrically active materials upon which neurons readily grow. The fusogen poly(ethylene glycol) (PEG) has been shown to improve outcomes after cervical and dorsal spinal cord transection. The long and narrow PEGylated graphene nanoribbon stacks (PEG-GNRs) with their 5 μm × 200 nm × 10 nm dimensions can provide a scaffold upon which neurons can grow and fuse. We disclose here the extensive characterization data for the PEG-GNRs.Methods:PEG-GNRs were chemically synthesized and chemically and electrically characterized.Results:The average aspect ratio of the PEG-GNRs was determined to be ~85, which corresponds to a critical percolation value (the point where insulating material becomes conductive by addition of conductive particles) of 1%. However, there was not a sharp increase in AC conductivity at frequencies relevant to action potentials.Conclusion:A robust characterization of PEG-GNRs is discussed, though the precise origin of efficacy in improving outcomes following spinal cord transection is not known.

Spinal cord fusion with PEG-GNRs (TexasPEG): Neurophysiological recovery in 24 hours in rats.

Background:The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, for the first time, we report the effects of locally applied water-soluble, conductive PEG(polyethylene glycol)ylated graphene nanoribbons (PEG-GNRs) on neurophysiologic conduction after sharp cervical cord transection in rats. PEG-GNRs were produced by the polymerization of ethylene oxide from anion-edged graphene nanoribbons. These combine the fusogenic potential of PEG with the electrical conducting properties of the graphene nanoribbons.Methods:Laminectomy and transection of cervical spinal cord (C5) was performed on Female Sprague-Dawley (SD) rats. After applying PEG-GNR on the severed part, electrophysiological recovery of the reconstructed cervical spinal cord was confirmed by somatosensory evoked potentials (SSEPs) at 24 h after surgery.Results:While no SSEPs were detected in the control group, PEG-GNR treated group showed fast recovery of SSEPs at 24 h after the surgery.Conclusion:In this preliminary dataset, for the first time, we report the effect of a novel form of PEG with the goal of rapid reconstruction of a sharply severed spinal cord.

Patterns of Phrenic Nerve Discharge after Complete High Cervical Spinal Cord Injury in the Decerebrate Rat.

Studies conducted since the second half of the 19th century have revealed spontaneous as well as pharmacologically induced phasic/rhythmic discharge in spinal respiratory motor outputs of cats, dogs, rabbits, and neonatal rats following high cervical transection (Tx). The extent to which these various studies validate the existence of a true spinal respiratory rhythm generator remains debated. In this set of studies, we seek to characterize patterns of spontaneous phasic/rhythmic, asphyxia-induced, and pharmacologically induced activity occurring in phrenic nerve (PhN) discharge after complete high cervical (C1-C2) spinal cord transection. Experiments were performed on 20 unanesthetized decerebrate Sprague-Dawley adult male rats. Patterns of spontaneous activity after spinalization included tonic, phasic, slow oscillatory, and long-lasting tonic discharges. Topical application of antagonists of GABAA and glycine receptors to C1- and C2- spinal segments induced left-right synchronized phasic decrementing activity in PhN discharge that was abolished by an additional C2Tx. Asphyxia elicited increases in tonic activity and left-right synchronized gasp-like bursts in PhN discharge, demonstrating the presence of spinal circuits that may underlie a spinal gasping-like mechanism. We conclude that intrinsic slow oscillators and a phasic burst/rhythm generator exist in the spinal cord of the adult rat. If present in humans, this mechanism may be exploited to recover respiratory function in patients sustaining severe spinal cord injury.

Pediatric arrowshot injury to cervical spinal cord-sagittal cord transection with no neurological deficit and good outcome: case report and review of literature

BackgroundPenetrating spinal cord injuries (PSCI) in cervical region are extremely rare in children. They mostly occur in a mechanism of a gunshot or a stab injury with the use of sharp objects. Gunshot injuries are usually fatal or end up with tetraplegia. Stab wounds may be less severe and result in partial neurological syndrome. In the management of PSCI in children, reliable diagnostics and history of the patient are the most valuable for further decisions, which include early or delayed exploration either nonsurgical treatment. There exist no clear algorithm for antibiotic use in pediatric population—it depends on the site of an injury, presence of pathological secretion from the wound, and nature of the trauma. The use of steroids is controversial. The most common complications related to surgery include infections, edema, and hemorrhage. They may also be associated with the migration of small residual microtraumatizing agent. The literature lacks algorithms for management in children.DiscussionIn this paper, an unusual case of almost total sagittal cervical cord transection is reported. The patient had no neurological symptoms and recovered with no complications. Diagnostic imaging on admission included X-ray and computed tomography. The patient underwent early surgical intervention with removal of foreign body from the cord and subsequent dural suturing. In the paper, the role of detailed history taking, adequate imaging, and drugs administration is discussed. The choice of distinct strategies is analyzed, and a revised literature review is presented in order to unify the management algorithm for pediatric PSCI.

Influence of personal preferences for life-sustaining treatment on medical decision making among pediatric intensivists*

Withholding and withdrawal of life-sustaining treatment by physicians is influenced by a variety of factors; the role of physicians' personal preferences for life-sustaining treatments has not previously been explored. We sought to examine the relationship between personal preferences for life-sustaining treatment and medical decision making among pediatric intensivists. Cross-sectional national anonymous mail survey. All board-certified/eligible pediatric intensivists identified by the American Medical Association Masterfile. None. A total of 471 (30%) surveys were returned. A Personal Preference Score was calculated from responses to personal-preference questions for life-sustaining treatments adapted from "Your Life, Your Choices," by Pearlman et al. Physicians were asked to consider the "acceptability" of offering and recommending treatment options involving life-sustaining treatments in a hypothetical scenario of a 2-yr old with a high cervical spinal-cord transection. Logistic regression controlling for sociodemographic characteristics found significant relationships (p<.01) between physicians' own preferences modeled as a one standard deviation change in their own Personal Preference Score (preference for life-sustaining treatment) and whether they offered more or less aggressive care (OR [95%CI]). Physicians who had a higher Personal Preference Score (higher preference for their own life-sustaining treatment) were more likely to recommend a tracheostomy (1.38 [1.35-1.41]) and reintubation if the patient failed extubation (1.87 [1.81-1.94]). Pediatric intensivists who had a lower Personal Preference Score (lower preference for life-sustaining treatment) were more likely to recommend that the patient not be reintubated if extubation failed (1.42 [1.39-1.46]) and to recommend Do Not Resuscitate status (1.34 [1.31-1.37]). Among pediatric intensivists, personal preferences for life-sustaining treatment were significantly associated with scenario-based responses to acceptability of withholding and withdrawal of life-sustaining treatment. Physicians should be aware of the potential for personal preferences to influence practice recommendations, and endeavor to elicit and respect family preferences in collaborative decision making.

Traumatic Cervical Cord Transection without Facet Dislocations-A Proposal of Combined Hyperflexion-Hyperextension Mechanism: A Case Report

A patient is presented with a cervical spinal cord transection which occurred after a motor vehicle accident in which the air bag deployed and the seat belt was not in use. The patient had complete quadriplegia below the C5 level and his imaging study showed cervical cord transection at the level of the C5/6 disc space with C5, C6 vertebral bodies and laminar fractures. He underwent a C5 laminectomy and a C4-7 posterior fusion with lateral mass screw fixation. Previous reports have described central cord syndromes occurring in hyperextension injuries, but in adults, acute spinal cord transections have only developed after fracture-dislocations of the spine. A case involving a post-traumatic spinal cord transection without any evidence of radiologic facet dislocations is reported. Also, we propose a combined hyperflexion-hyperextension mechanism to explain this type of injury.

Temperature and Vascular Volume Effects on Gastric Ulcerogenesis After Cord Transection

Gastric ulcers are an important cause of morbidity and mortality in the critically ill, especially those with CNS injury. We used cervical spinal cord transection (CCT) in the rat to model these ulcers and examined the effect of core body temperature and vascular volume on gastric ulcerogenesis. Hypothermia significantly increased ulcerogenesis compared to euthermia, while maintained euthermia produced ulcer indices not different from sham surgery. Hypovolemia (10% blood volume withdrawal) significantly increased ulcerogenesis compared to hypervolemia (10% of blood volume crystalloid infusion) or sham surgery. These results support crystalloid infusion and maintenance of core body temperature in the clinical setting.

Tonic glutamatergic drive of RVLM vasomotor neurons?

the rostral ventrolateral medulla (RVLM) plays a critical role in the maintenance of baseline arterial pressure (AP) in all species in which it has been examined, and it appears to be the primary site responsible for the tonic supraspinal drive of sympathetic vasomotor outflow and AP, at least in

Fractal activity generated independently by medullary sympathetic premotor and preganglionic sympathetic neurons.

In anesthetized cats with cervical spinal cord transection, Fano factor analysis was used to test for time-scale invariant (fractal) fluctuations in spike counts of single preganglionic cervical sympathetic neurons (PSNs) and putative sympathetic premotor neurons located in the rostral ventrolateral medulla (RVLM) and caudal medullary raphe. The medullary neurons exhibited cardiac-related activity, and their axons projected to the spinal cord, as demonstrated by antidromic activation. The variance-to-mean spike count ratio (Fano factor) was plotted as a function of the window size used to count spikes. The Fano factor curves for seven PSNs, eight RVLM neurons, and eight raphe neurons contained a power law relationship extending over more than one time scale. In these cases, random shuffling of the interspike intervals in the original time series eliminated the power law relationship. Thus the power law relationships can be attributed to long-range correlations among interspike intervals rather than simply to the distribution of the intervals that is not changed by shuffling the data. It is concluded that PSNs and sympathetic premotor neurons in the medulla can independently generate fractal firing patterns.

Microinjection of bombesin into the ventrolateral reticular formation inhibits peripherally stimulated gastric acid secretion through spinal pathways in rats

Bombesin injected into the cisterna magna potently inhibits gastric acid secretion stimulated by intravenous infusion of pentagastrin. Sites in the medulla oblongata where bombesin acts to suppress gastric acid secretion were investigated in urethane-anesthetized rats with gastric cannula. Bombesin or vehicle was injected into the medullary parenchyma or intracisternally (i.c.) 60 min after the start of an intravenous pentagastrin infusion; gastric acid secretion was monitored every 10 min for 20 min before and 150 min after the start of pentagastrin. Bombesin (0.2, 0.6 or 6.2 pmol) microinjected into the ventrolateral reticular formation (VLRF) inhibited dose-dependently the net acid response to pentagastrin by 40.8±11.1, 75.4±12.8 and 96.7±19.4%, respectively, at the 40–50 min period after microinjection compared with the vehicle group. Bombesin action in the VLRF was long lasting (96% inhibition still observed at 90 min after 6.2 pmol), and completely abolished by cervical spinal cord transection at the C6 level. By contrast, bombesin injected i.c. at 0.2 or 0.6 pmol had no effect while at 6.2 pmol, there was a 79.0±3.9% peak inhibition of pentagastrin-stimulated acid secretion. Bombesin (6.2 pmol) injected into the dorsal motor nucleus reduced the acid response to pentagastrin by 29%. The parvicellular and gigantocellular reticular nuclei were not responsive to bombesin. These results indicate that bombesin acts in the VLRF to inhibit pentagastrin-stimulated gastric acid secretion through spinal pathways, suggesting a potential role of medullary VLRF area in the sympathetic control of gastric acid secretion.

Complete cervical or thoracic spinal cord transections delay gastric emptying and gastrointestinal transit of liquid in awake rats

To determine the changes on gastric emptying and gastrointestinal transit of liquid throughout the first week after spinal cord transection (SCT) in rats. Male Wistar rats (n=121) were fasted for 16 h and a complete SCT or laminectomy was performed between C7 and T1 (cervical group) or between T4 and T5 (thoracic group). Dye recovery in the stomach, proximal, mid and distal small intestine was determined 30 min, 6 h, 1, 3 or 7 days after surgery. The test meal (1.5 ml of a phenol red solution, 0.5 mg/ml in 5% glucose) was intragastrically administered and the animals sacrificed by cervical dislocation 10 min later. Cervical SCT increased dye recovery in the stomach (P<0.05) by 70.1, 78.7, 34.2, 41.3 and 50.9% while it decreased recovery in the mid small intestine (P<0.05) by 87.1, 85.1, 74.8, 59.5 and 80.1%, respectively 30 min, 6 h, 1, 3 and 7 days after SCT. Thoracic SCT increased gastric recovery (P<0.05) by 43.5, 67.6, 51.2, 75.4 and 38. 9% while it decreased recovery in the mid small intestine (P<0.05) by 100, 100, 45.6, 100 and 66.6%, respectively 30 min, 6 h, 1, 3 and 7 days after SCT. A separate group was submitted to laminectomy+bilateral sciatic nerve transection (paraplegic sham). Gastric emptying and gastrointestinal transit were not inhibited in this group. In summary, gastric emptying and gastrointestinal transit of liquid are inhibited throughout the first week after high SCT in awake rats.

Effect of intracisternal thyrotropin-releasing hormone on hepatic blood flow in rats.

Central neuropeptides play a role in many physiological regulatory processes through the autonomic nervous system. Thyrotropin-releasing hormone (TRH) is distributed in the central nervous system and acts as a neurotransmitter to regulate gastric functions through vagal-muscarinic pathways. The central effect of the TRH analog on hepatic blood flow was investigated in urethan-anesthetized rats. Hepatic blood flow was determined by the hydrogen gas clearance technique. Intracisternal injection of the stable TRH analog RX-77368 (5-100 ng) dose dependently increased hepatic blood flow with peak response at 15 min after the peptide was administered (net change from basal for vehicle and 5, 10, 100, and 500 ng RX-77368 was 2.0 +/- 0.2, 8.9 +/- 0.8, 19.4 +/- 2.6, 32.6 +/- 3.3, and 28.5 +/- 6.8 ml.min-1.100 g-1, respectively), and this stimulatory effect returned to baseline at 90 min. The stimulation of hepatic blood flow by the intracisternally administered TRH analog was abolished by atropine methyl nitrate (0.15 mg/kg ip), indomethacin (5 mg/kg ip), NG-nitro-L-arginine methyl ester (10 mg/kg iv), and hepatic branch vagotomy but not by cervical spinal cord transection (C6 level). Intravenous injection of RX-77368 did not have any effect on hepatic blood flow. These results indicate that TRH acts in the central nervous system to stimulate hepatic blood flow through vagal-muscarinic and indomethacin- and nitric oxide-dependent pathways.

Intravenous morphine increases release of nitric oxide from spinal cord by an alpha-adrenergic and cholinergic mechanism.

Systemic opioids produce analgesia in part by activating bulbospinal noradrenergic pathways. Spinally released norepinephrine (NE) has been suggested to produce analgesia in part by stimulating alpha2-adrenoceptors on cholinergic spinal interneurons to release acetylcholine (ACh). We hypothesized that this spinally released ACh would stimulate synthesis of nitric oxide (NO), and that spinally released NO after intravenous (IV) opioid injection thus would depend on a cascade of noradrenergic and cholinergic receptor stimulation. To test these hypotheses, IV morphine was administered to anesthetized sheep, and neurotransmitters in dorsal horn interstitial fluid were measured by microdialysis. IV morphine increased NE and ACh in dorsal horn microdialysates, and these increases were inhibited by IV naloxone or cervical spinal cord transection. IV morphine also increased dorsal horn microdialysate concentrations of nitrite, a stable metabolite of NO. Increases in NE, ACh, and nitrite were antagonized by prior intrathecal injection of the alpha2-adrenergic antagonist idazoxan, the muscarinic antagonist atropine, or the NO synthase inhibitor N-methyl--arginine (NMLA). To examine the concentration-dependent effects of spinal adrenergic stimulation, isolated rat spinal cord tissue was perfused with the alpha2-adrenergic agonist clonidine. Clonidine increased nitrite in the spinal cord tissue perfusate, an effect blocked by coadministration of idazoxan, atropine, and NMLA. These data support a previously hypothesized cascade of spinally released NE and ACh after systemic opioid administration. These data also suggest that spinally released NO plays a role in the analgesic effects of systemic opioids. In addition, these data imply a positive feedback whereby spinally released nitric oxide increases NE release and that has not previously been described.

Cardiovascular effects of anandamide in anesthetized and conscious normotensive and hypertensive rats.

We previously showed that in anesthetized rats anandamide elicits bradycardia and a triphasic blood pressure response: transient hypotension secondary to a vagally mediated bradycardia, followed by a brief pressor and prolonged depressor response, the latter two effects being similar to those of delta 9-tetrahydrocannabinol (THC). The prolonged depressor but not the pressor response was reduced after alpha-adrenergic receptor blockade or cervical spinal cord transection and was inhibited by the cannabinoid type 1 (CB1) receptor antagonist SR141716A, suggesting CB1 receptor-mediated sympathoinhibition as the underlying mechanism. Here we examined the relationship between sympathetic tone and the cardiovascular effects of anandamide by testing these effects in both conscious and anesthetized, normotensive and spontaneously hypertensive rats. In urethane-anesthetized normotensive rats, SR141716A inhibited the prolonged depressor and bradycardic effects of anandamide and THC with similar potency, whereas it did not affect the pressor response to either agent. Anadamide caused similar hypotension in spontaneously breathing and in paralyzed, mechanically ventilated rats, suggesting that the hypotension is not secondary to respiratory effects. In conscious normotensive rats, anandamide elicited transient vagal activation and a brief pressor response, but the prolonged hypotensive component was absent. SR141716A potentiated and prolonged the brief pressor response to anandamide, suggesting that the depressor response may have been masked by an increased pressor response. All three phases of the anadamide response were present in both anesthetized and conscious spontaneously hypertensive rats, and the hypotensive component, inhibited by SR141716A in both, was more prolonged in the absence (> 50 minutes) than the presence (10 to 15 minutes) of anesthesia. We conclude that anandamide causes a non-CB1 receptor-mediated pressor and a CB1 receptor-mediated prolonged depressor response. The depressor response can be elicited in both conscious and anesthetized animals, but its magnitude depends on preexisting sympathetic tone.

Effects of mechanical factors on growth and maturation of the lung in fetal sheep.

Previous fetal studies indicated that endocrine factors control surfactant maturation, whereas mechanical forces affect lung growth, but not surfactant. We altered mechanical forces in fetal sheep lungs at 100-108 days gestation by tracheal ligation (TL, n = 15, 7 successful studies) to accelerate lung growth, transection of cervical spinal cord (TCSC, n = 17, 6 successful studies) to produce lung hypoplasia, or sham operation (n = 11, 6 successful studies). The reasons for the high mortality rates are not known. At delivery (130-142 days), groups were similar in gestational age, weight, and cortisol. Effects on lung growth were similar to, but effects on surfactant differed from, previous reports. TL increased lung growth but decreased saturated phosphatidylcholine (SatPC) and surfactant protein (SP)A and apparently decreased SP-B and relative numbers of alveolar type II cells (based on immunohistochemical studies of 1 animal in each group); TCSC had opposite effects. In contrast to a previous study (J. A. Kitterman, G. C. Liggins, G. A. Campos, J. A. Clements, C. S. Forster, C. H. Lee, and R. K. Creasy, J. Appl. Physiol, 51: 384-390, 1981), SatPC did not correlate with cortisol. We conclude that altering mechanical forces in fetal lung affects not only lung growth but also surfactant maturation and possibly alveolar epithelial differentiation and disturbs the normal correlation between cortisol and surfactant. Associated changes in insulin-like growth factor I (IGF-I; increased by TL, P = 0.003) suggest a possible role for IGF-I in these effects.

An In Vitro Brainstem-Heart Preparation of the Neonatal Rat with Intact Right Vagus Nerve.

An in vitro brainstem preparation of the neonatal rat with intact right vagal (X) innervation of the right atrium, and intact medullary roots of the left X and glossopharyngeal (IX) nerves for stimulation was developed. The preparation was continuously superfused with artificial CSF at 25 degrees C. The electrical activity of the right atrium was recorded to determine the heart rate. Applications of atropine or propranolol to the superfusate did not alter the heart rate. Electrical stimulation (0.5 ms pulse, 20 Hz) of the left IX and X afferents elicited a reduction in the heart rate from 70.3 +/- 13.2 to 50.6 +/- 13.2 beats/min (mean +/- SD, p < 0.05), which was abolished after division of the right X or application of atropine to the superfusing solution. A similar reflex bradycardia was seen in a preparation with intact left vagal-right atrium innervation during right IX and X afferent stimulation. Cervical spinal cord transection affected neither the baseline heart rate nor the magnitude of the reflex bradycardia. Longitudinal sectioning of the medulla oblongata in the mid-line down to the level of the posterior inferior cerebellar artery abolished the heart rate response. After bilateral cervical vagotomies, electrical stimulation (0.5 ms pulse, 20 Hz, up to 100 microA) of the ventrolateral medulla oblongata, lateral funiculus at C2 or intermediate nucleus of the spinal cord at Th1-4 did not affect the heart rate. These results indicate that the functions in the lower brainstem are preserved in this preparation, at least in regard to the generation of reflex bradycardia. The results also suggest that the laterality of cardiac vagal innervation and sympathetic innervation will develop during the postnatal period. This preparation may be useful for the study of the central neuronal network controlling the heart rate.