Caudal Sites Research Articles

Stimulation of the rat medullary raphe nuclei induces differential responses in respiratory muscle activity

Neural control circuits that coordinate the motor activity of the diaphragm (DIA) and the geniohyoid muscle (GH) are potentially involved in pathological conditions such as various forms of sleep apnea. Here we investigated a differential role of the raphe magnus (RMg), pallidus (RPa) and the obscurus (ROb) nuclei in the neural control of DIA and GH muscle activity in rats under volatile anesthesia. In order to characterize a topographical organization of the raphe nuclei we analyzed changes in DIA and GH during high-frequency stimulation (HFS, 10-130 Hz, 60 micros pulse width, 40-160 microA, 30s). HFS of the RMg and the ROb induced apnea, in the latter case apnea was associated with massive tonic discharge in the GH. By contrast, HFS of the RPa induced tachypnea. At caudal stimulation sites the tachypnea was accompanied by tonic DIA activity and cessation of GH. These data suggest a differential distribution of inhibitory and excitatory drives of DIA and GH muscles within distinct raphe nuclei.

Coexistence of a human tail and congenital dermal sinus associated with lumbosacral lipoma

We present a female baby with a human tail associated with congenital dermal sinus (CDS) at the caudal site of the tail. Magnetic resonance (MR) images with constructive interference in steady-state (CISS) sequencing clearly demonstrated a lumbosacral lipoma of caudal type, contiguous with the dermal sinus tract and not with the human tail. At 3 months old, the tail was surgically removed. The dermal sinus tract and contiguous lipoma were also resected, and untethering of the spinal cord was performed. Although both the human tail and CDS are frequently associated with spina bifida occulta, coexistence of the tail and CDS is exceedingly rare. CISS-MRI is useful for demonstrating the precise anatomical relationship between these complicated pathologies.

Trephination of the Equine Rostral Maxillary Sinus: Efficacy and Safety of Two Trephine Sites

To examine 2 rostral maxillary sinus (RMS) trephine sites for safety and efficacy using skulls of horses of varying age. Descriptive study. Cadaveric equine skulls (n=40). Two RMS trephination sites (rostral, caudal) were made in each skull. Radiographic projections using markers at each site were used to determine if sites were within the RMS and directly overlying a cheek tooth. Sinusotomy in 14 skulls was used to determine correlation between radiographic and anatomic location of trephine sites, and of the rostrolateral aspect of the maxillary septum. Age-related risk of trephine site being directly over a cheek tooth was determined using logistic regression. Trephine site was within the RMS in 98% of skulls using the rostral portal and 68% using the caudal portal. The rostral site was over a cheek tooth in 18% of skulls compared with 10% using the caudal site. There was a significant negative relationship between the trephine site overlying a tooth and horse age for rostral (P=.02) and caudal (P=.03) sites. The radiographic appearance of the maxillary septum correlated to the rostrolateral portion of the septum in 12 of 14 skulls that had sinusotomy. The rostral RMS trephine portal is more reliable than the caudal site for entering the RMS. Horses <or=5 years are at high risk for the trephine site overlying a cheek tooth and we advise that RMS trephination in this age group be performed with radiographic guidance.

The Difference of Contrast Effects of Myelography in Normal Dogs: Comparison of Iohexol (180mgI/ml), Iohexol (240mgI/ml) and Iotrolan (240mgI/ml)

The contrast effects of three different contrast media preparations (iohexol 180 mgI/ml, iohexol 240 mgI/ml and iotrolan 240 mgI/ml) in conventional and CT myelography were compared. Three beagle dogs were used and the study employed a cross-over method (total of 9) for each contrast media. The result of CT myelography showed that the contrast effect of iohexol (180 mgI/ml), which had low viscosity, was highest in cranial sites, and the contrast effect of high-viscosity iotrolan (240 mgI/ml) was highest in caudal sites 5 min after injection of the contrast media preparations. This shows that the diffusion of contrast media preparations in the subarachnoid space is influenced by viscosity. The results of conventional myelography also showed that the diffusion of contrast media preparations is influenced by viscosity. Therefore, it is important to identify the location of spinal lesions in veterinary practice, and low viscosity contrast medium preparation with wide spread contrast effects is considered suitable for myelography.

Functional topography of the dorsomedial hypothalamus

The dorsomedial hypothalamus (DMH) has been proposed to play key roles in both the defense reaction to acute stress and in the thermoregulatory response to cold. We reasoned that the autonomic/respiratory motor patterns of these responses would be mediated by at least partly distinct DMH neuron populations. To test this, we made simultaneous recordings of phrenic nerve and plantar cutaneous vasoconstrictor (CVC) activity in 14 vagotomized, ventilated, urethane-anesthetized rats. Microinjections of d,l-homocysteic acid (DLH; 15 nl, 50 mM) were used to cause localized, short-lasting (<1 min) activation of DMH neuron clusters. Cooling the rat's trunk skin by perfusing cold water through a water jacket-activated plantar CVC activity but depressed phrenic burst rate (cold-response pattern). The expected "stress/defense response" pattern would be phrenic activation, with increased blood pressure, heart rate, and possibly CVC activity. DLH microinjections into 76 sites within the DMH region never reduced phrenic activity. They frequently increased phrenic rate and/or plantar CVC activity, but the magnitudes of those two responses were not significantly correlated. Plantar CVC responses were evoked most strongly from the dorsal hypothalamic area and most dorsal part of the dorsomedial nucleus, whereas peak phrenic rate responses were evoked from more caudal sites; their relative magnitudes varied systematically with rostrocaudal position. Tachycardia correlated with plantar CVC responses but not phrenic rate. These findings indicate that localized activation of DMH neurons does not evoke full "cold-response" or stress/defense response patterns, but they demonstrate the existence of significant functional topography within the DMH region.

Chaetal arrangement in Orbiniidae (Annelida, Polychaeta) and its significance for systematics

The systematic position of Orbiniidae within Polychaeta is still uncertain. In order to provide additional comparative data, we investigated the chaetal arrangement in this family, which is considered valuable for polychaete systematics. Specimens of Scoloplos armiger, Orbinia latreillii, and Pettibonella multiuncinata were examined by SEM and serial sections analysed by computer aided 3D-reconstructions. The obtained data suggest that the chaetal arrangement of Orbiniidae resembles that of other sedentary polychaetes in only a few respects. Transverse rows are only present in the main, anterior part of the chaetal patches of thoracic neuropods. The position of the formative site indicates homology with the transverse rows of several sedentary polychaete taxa. The chaetal patches thus differ significantly from those known in Apistobranchidae. Independent rows with an own caudal formative site, which run along the caudoventral edge of the chaetal patches, resemble the neuropodial ventral longitudinal rows known in Spionidae and related taxa. The abdominal neuropodia of S. armiger and O. latreillii bear longitudinal rows of chaetae. These are reorientated during ontogenetic chaetiger transformation and become the transverse rows of the thoracic chaetal patches. 3D reconstruction of S. armiger revealed that the notopodial chaetal bundles are organized in rows as well. Notopodia and abdominal neuropodia bear deep reaching supportive chaetae. They are the first chaetae formed during neuropodial development and reside dorsally to the longitudinal row of capillary chaetae. Neither position nor structure indicates homology with the supportive chaetae of other sedentary polychaetes. Spionidae and related taxa are thus the only sedentary polychaetes, which specifically resemble Orbiniidae in certain aspects of their chaetal arrangement.

Transplantation of Adult Rat Spinal Cord Stem/Progenitor Cells for Spinal Cord Injury

Stem/progenitor cells derived from the ependymal region of the spinal cord have the ability to self-renew and are multipotential for neurons and glia. These cells may have the ability to regenerate the injured mammalian spinal cord as they do in some lower vertebrates. However, the optimal conditions for transplantation and the fate of transplanted cells are not fully known. In the current study, spinal cord stem/progenitor cells were cultured from adult male rats expressing enhanced green fluorescent protein (eGFP). Neurospheres were transplanted at the time of clip compression injury (35-g force) into the injury site, or 1 mm rostral and caudal to the injury site. Neurospheres were also transplanted into a subacute model (day 9 after injury) and a chronic model (day 28 after injury). Functional recovery was also studied in an acute injury model with weekly locomotor testing over a 16-week period. A significant increase in cell survival at 7 days was seen in rats receiving rostral and caudal injections as compared to injection directly into the site of injury. A significant increase in cell survival was also seen in rats receiving subacute transplants at 9 days after injury. Transplanted cells differentiated primarily into astrocytes (31.2%) and oligodendrocytes (50.3%), and a small number of neurons (1%). No improvement was seen in the Basso, Beattie and Bresnahan (BBB) locomotor rating scale after acute transplantation as compared with injury only, although surviving transplanted cells were identified that had migrated across the injury site from the rostral and caudal injection sites.

Caudal Spine Shedding Periodicity and Site Fidelity of Round Stingrays, Urobatis halleri (Cooper), at Seal Beach, California: Implications for Stingray-related Injury Management

Abstract Natural caudal spine replacement rates, population size and site fidelity of round stingrays, Urobatis halleri (Cooper), at Seal Beach, California were determined to evaluate the efficacy of clipping of caudal spines of stingrays to reduce injury to human beachgoers. Of the 2,183 stingrays caught, clipped, tagged, and released at Seal Beach, only 13 (0.06%) were recaptured over a three-year period, indicating a large, mobile population. Natural spine replacement occurred between August–October, when a majority of rays were found with two spines. Monthly catch rates of rays were variable, but positively correlated with the number of injuries reported by beachgoers. There was no significant reduction in stingray-related injuries to beach goers at Seal Beach over the period when stingray caudal spine clipping was conducted.

Kinematics and eye–head coordination of gaze shifts evoked from different sites in the superior colliculus of the cat

Shifting gaze requires precise coordination of eye and head movements. It is clear that the superior colliculus (SC) is involved with saccadic gaze shifts. Here we investigate its role in controlling both eye and head movements during gaze shifts. Gaze shifts of the same amplitude can be evoked from different SC sites by controlled electrical microstimulation. To describe how the SC coordinates the eye and the head, we compare the characteristics of these amplitude-matched gaze shifts evoked from different SC sites. We show that matched amplitude gaze shifts elicited from progressively more caudal sites are progressively slower and associated with a greater head contribution. Stimulation at more caudal SC sites decreased the peak velocity of the eye but not of the head, suggesting that the lower peak gaze velocity for the caudal sites is due to the increased contribution of the slower-moving head. Eye-head coordination across the SC motor map is also indicated by the relative latencies of the eye and head movements. For some amplitudes of gaze shift, rostral stimulation evoked eye movement before head movement, whereas this reversed with caudal stimulation, which caused the head to move before the eyes. These results show that gaze shifts of similar amplitude evoked from different SC sites are produced with different kinematics and coordination of eye and head movements. In other words, gaze shifts evoked from different SC sites follow different amplitude-velocity curves, with different eye-head contributions. These findings shed light on mechanisms used by the central nervous system to translate a high-level motor representation (a desired gaze displacement on the SC map) into motor commands appropriate for the involved body segments (the eye and the head).

Neutralization of ciliary neurotrophic factor reduces astrocyte production from transplanted neural stem cells and promotes regeneration of corticospinal tract fibers in spinal cord injury

Transplantation of neural stem cells (NSC) into lesioned spinal cord offers the potential to increase regeneration by replacing lost neurons or oligodendrocytes. The majority of transplanted NSC, however, typically differentiate into astrocytes that may exacerbate glial scar formation. Here we show that blocking of ciliary neurotrophic factor (CNTF) with anti-CNTF antibodies after NSC transplant into spinal cord injury (SCI) resulted in a reduction of glial scar formation by 8 weeks. Treated animals had a wider distribution of transplanted NSC compared with the control animals. The NSC around the lesion coexpressed either nestin or markers for neurons, oligodendrocytes, or astrocytes. Approximately 20% fewer glial fibrillary acidic protein-positive/bromodeoxyuridine (BrdU)-positive cells were seen at 2, 4, and 8 weeks postgrafting, compared with the control animals. Furthermore, more CNPase(+)/BrdU(+) cells were detected in the treated group at 4 and 8 weeks. These CNPase(+) or Rip(+) mature oligodendrocytes were seen in close proximity to host corticospinal tract (CST) and 5HT(+) serotonergic axon. We also demonstrate that the number of regenerated CST fibers both at the lesion and at caudal sites in treated animals was significantly greater than that in the control animals at 8 weeks. We suggest that the blocking of CNTF at the beginning of SCI provides a more favorable environment for the differentiation of transplanted NSC and the regeneration of host axons.

Tensile Strength Comparison of Small Intestinal Submucosa Body Wall Repair

Porcine small intestinal submucosa (SIS) has been studied for body wall repair. However, the best method to implant the biological material has not been investigated. The objective of this study was to compare tensile strengths achieved after healing when SIS was placed using three implant techniques (onlay, inlay, underlay) in a porcine model of abdominal wall defect. Twenty female domestic pigs had three abdominal midline sites assigned to one of five test groups: SIS implantation using inlay, onlay, or underlay technique; sham surgery (sutured midline incision) or normal body-wall control. Full-thickness muscle/fascia midline abdominal defects (6 x 4 cm) were surgically created and then repaired using eight-layer SIS. Healing was evaluated at 1 and 4 post-operative months by tensile strength testing and histopathology. Hernias were not observed. Tensile strengths were not statistically different between the five test groups (P = 0.39) or between months 1 and 4 (P = 0.35). The caudal site was stronger than the cranial or middle sites in the 1 month group (P < 0.0001). Histologically, healing appeared to progress over time as the repair site showed remodeling towards an interlacing fibrous connective tissue pattern. No significant differences in tensile strength were found between implant techniques and were not statistically different from sham surgery and normal control tissue. This study suggested that SIS healing/remodeling provides sufficient tensile strength for the repair of ventral (anterior) abdominal wall defects when implanted using any of three common techniques.

Secondary spinal cord hypoperfusion of circumscribed areas after injury in rats

Objectives: The evaluation of the spatial spread of ischemia following spinal cord injury (SCI) is important for planning therapeutic strategies for secondary injury. The purpose of this study was to investigate in detail the change in regional spinal cord blood flow (rSCBF) after SCI.Methods: Thirty-four male Wistar rats were used, for which laminectomies of the T11–13 vertebrae were performed. SCI was produced by a directed impact through a laminectomy site at the level of the Th12 using a pneumatic impact device. We measured the sequential and spatial changes of rSCBF using a laser Doppler scanning technique before and after SCI in rats not only at the injured myelomere but also at the circumferent myelomeres. SCBF mapping was carried out before and after SCI on each site.Results: After SCI, the rSCBF value gradually decreased for each site for the SCI group (n=26), while it globally decreased at the epicenter. Moreover, a decrease in SCBF was observed at the caudal and rostral sites. The mean value of the %SCBF 120 minutes after SCI for each site was 63.6±2.3% (Th11), 74.4±4.5% (Th12), 75.8±3.2% (Th13), and was significantly lower for the rostral site compared with the caudal site (p<0.05, one-way analysis of variance).Discussion: This study found that SCBF is significantly decreased not only at the injured myelomere but also at the circumferent myelomeres. Circumferentially extending ischemia after SCI is related to secondary injury after SCI. The improvement in SCBF after SCI, therefore, can be attributed to the treatment of SCI.

Localization and Connectivity in Spinal Interneuronal Networks: The Adduction–Caudal Extension–Flexion Rhythm in the Frog

We have previously reported that focal intraspinal N-methyl-d-aspartate (NMDA) iontophoresis in the frog elicits a motor output, which is organized in terms of its constituent isometric force directions at the ipsilateral ankle and its topography. Furthermore, the associated EMG patterns can be reconstructed as the linear combinations of seven muscle synergies, labeled A to G. We now focus on one of the most common NMDA-elicited outputs, the adduction-caudal extension-flexion rhythm, and examine the relationship between the different force phases in terms of synergies and topography. Two distinct EMG patterns produce caudal extensions, and only one of the two patterns is used at most sites. The key synergy combinations for the two patterns are B + e and D + c (strongest synergies capitalized). These two patterns map at distinct locations in the lumbar cord. Within individual sites rhythms, we find linkages among the synergies used to produce adductions, the onsets of flexions after caudal extensions, and the synergy pattern producing the caudal extensions. For example, the synergy composition of adductions at B + e caudal extension sites is dominated by E + b and at D + c caudal extension sites by C + d. The two types of adductions map at distinct locations, situated between the two caudal extension regions. Specifically the linked patterns of caudal extension-adduction interleave rostrocaudally in a CE2-ADD1-ADD2-CE1 sequence, where 1 and 2 refer to the two pattern types. The implications of this topography and connectivity with respect to motor systems organization and behaviors are discussed.

Engraftment and differentiation of neocortical progenitor cells transplanted to the embryonic brain in utero.

Transplantation of neural progenitors or stem cells is a most useful tool to investigate the relative contribution of cell-autonomous mechanisms and environmental cues in the regulation of cell specification and differentiation during CNS development. To assess the capability of neocortical progenitor cells to integrate into foreign brain regions, here we examined the fate of precursor cells isolated from the dorsal telencephalon of E12 ss-actin-EGFP transgenic mouse embryos after heterotopic/heterochronic transplantation to the E16 rat brain in utero. Our observations show that donor cells were able to penetrate, survive and produce mature cell types into wide regions of the host CNS. Namely, EGFP-positive cells acquired site-specific neuronal identities in many telencephalic regions, including neocortex, hippocampus, olfactory bulb and corpus striatum. In contrast, incorporation into more caudal sites was much less efficient. A fraction of donor cells formed large aggregates that remained segregated from the host milieu. Such aggregates contained mature neurons and glia, including some EGFP-negative elements of host origin, and developed the complex organization of the mature nervous tissue. On the other hand, transplanted cells that engrafted in the parenchyma of extratelencephalic regions predominantly generated glial types. The few neurons failed to acquire obvious site-specific phenotypic traits and did not integrate into the local host architecture. Altogether, our observations indicate that E12 neocortical progenitors are already committed towards regional identities and are unable to modify their phenotypic choices when exposed to heterotopic environmental conditions along different rostro-caudal domains of the embryonic CNS.

Direct projections from caudal ventrolateral medullary depressor sites to the subfornical organ

Experiments were performed in the male Wistar rat to investigate the projections from cardiovascular responsive sites in the ventrolateral medulla (VLM) to the subfornical organ (SFO). Unilateral iontophoretic injections of Phaseolus vulgaris leucoagglutinin (PHA-L) were made into either caudal VLM (CVLM) sites at which microinjection of l-glutamate (10 nl; 0.25 M) elicited decreases in mean arterial pressure or into rostral VLM (RVLM) sites at which l-glutamate microinjection elicited increases in arterial pressure. After a survival period of 7–10 days, transverse sections of the forebrain and brainstem were processed for PHA-L immunoreactivity. After injections of PHA-L into the CVLM, axonal and presumptive terminal labeling was found bilaterally throughout the rostrocaudal extent of the SFO, although most of the projections were observed within the rostral half of the nucleus. Within the SFO, labeling was found primarily in the lateral aspects of the nucleus, often in close proximity to blood vessels. In addition, CVLM injections resulted in labeling within the organum vasculosum of the laminae terminalis (OVLT) and within the ventral and dorsal components of the median preoptic nucleus (MnPO) bilaterally, but with an ipsilateral predominance. In contrast, PHA-L injections into the RVLM did not result in axonal labeling in the SFO or OVLT, although a few labeled axons were found to course through the region of the ventral component of MnPO. These data have demonstrated that neurons within the cardiovascular responsive region of the CVLM send direct axonal projections to the SFO and other structures of the laminae terminalis, and suggest that the CVLM may function in the modulation of the activity of neurons of circumventricular organs to intra- and extracellular signals of body fluid balance.

Effect of Rapid Shallow Breathing on the Distribution of 18O-Labeled Ozone Reaction Product in the Respiratory Tract of the Rat

We examined the effect of breathing pattern on ozone reaction product content within the respiratory tract. Thirty-four anesthetized, male Wistar rats were exposed to oxygen-18 (18O)-labeled ozone at 1.0 ppm for 2 h using a dual-chamber, negative-pressure ventilation system. Frequency was set at 80 (n = 9), 120 (n = 7), 160 (n = 8), or 200 (n = 10) breaths per minute (bpm), while tidal volume (Vt) was set to provide a constant minute ventilation of 72.8 ml/min/100 g body weight. Airways sampled were from the midlevel trachea and the mainstem bronchi and parenchyma of the cranial and caudal right lobes. 18O content in each airway sample was quantified and normalized to surface area. Across frequencies, there was significantly greater (p <. 05) 18O content in the trachea and bronchi (conducting airway epithelium) compared to the parenchyma sampling sites. Tracheal 18O content decreased between 80 and 160 bpm, but then underwent an increase at 200 bpm. In comparison, 18O content gradually increased between 80 and 200 bpm at the right cranial and caudal bronchi sites. Right cranial parenchymal 18O content decreased at 200 bpm compared to 80, 120, and 160 bpm. Right caudal parenchymal 18O content was relatively constant over all breathing frequencies. We concluded that the development of rapid shallow breathing from 80 to 160 bpm results in a reduced deposition of O3 in the trachea, while only mildly affecting to ozone deposition in parenchyma supplied by short and long airway paths.

Changes of lymphatic flow in case of pancreatic duct obstruction in the pig--as a model of pancreatic cancer.

To investigate the lymph network change in pancreatic duct obstruction in pigs as a model of pancreatic cancer invading pancreatic duct, six domestic pigs weighing 17-40 kg underwent surgery as protocol. Two of them were controls, and the others underwent ligation of the pancreatic duct as a model of ductal obstruction. A CH 40 and lipiodol mixture was injected in their pancreas at 7 or 21 Days after first operation. Radiographic examination had been also performed. Five or 14 days later, they were examined radiographically, and sacrificed for histological examination. Ligation of the pancreatic duct caused experimental pancreatitis. Dilatation of the pancreatic duct and dilatation of the lymph canal in the interlobular space of pancreas was demonstrated in the ligation group. CH 40 and lipiodol showed discrepancies in the distribution. There were not distinct differences between the two groups in a route of CH 40 traveling. Only fluoroscopic examination revealed an image of lipiodol enlargement to the caudal site in the ligated group. The congestive lymph system may have impaired flow like reflux.

Hyperphagic effects of brainstem ghrelin administration.

The role of ghrelin in feeding control has been addressed from a largely hypothalamic perspective, with little attention directed at ingestive consequences of stimulation of the peptide's receptor, the growth hormone secretagogue receptor (GHS-R), in the caudal brainstem. Here, we demonstrate a hyperphagic response to stimulation of GHS-R in the caudal brainstem. Ghrelin (150 pmol) delivered to the third and fourth ventricles significantly and comparably increased cumulative food intake, with maximal response approximately 3 h after injection. The meal patterning effects underlying this hyperphagia were also similar for the two placements (i.e., significant reduction in the time between injection and first-meal onset, an increase in the number of meals taken shortly after the injection, and a trend toward an increase in the average size of the first meals that approached but did not achieve statistical significance). In a separate experiment, ghrelin microinjected unilaterally into the dorsal vagal complex (DVC) significantly increased food intake measured 1.5 and 3 h after treatment. The response was obtained with a 10-pmol dose, establishing the DVC as a site of action with at least comparable sensitivity to that reported for the arcuate nucleus. Taken together, the results affirm a caudal brainstem site of action and recommend further investigation into multisite interactions underlying the modulation of ingestive behavior by ghrelin.

GABAergic immunoreactivity is predominant in neurons derived from expanded human neural precursor cells in vitro

Neural precursor cells have been previously isolated from the developing human nervous system and their properties studied both in vitro and in transplantation paradigms in vivo. However, their ability to differentiate into neurons of different neurochemical phenotypes remains poorly defined. In this study, the default in vitro neuronal differentiation of hENPs derived from five different regions of the human embryonic brain (cerebral cortex, striatum, cerebellum, ventral mesencephalon, and spinal cord) was studied after varying periods of time in culture. The results were directly compared to those from similarly prepared murine ENPs. hENPs prepared from all five regions showed a significant reduction in the number of neurons generated at each passage, such that by passage 4 only between 5 and 10% of cells spontaneously adopted a neuronal phenotype after differentiation in vitro. A similar observation was obtained with murine ENPs. hENPs prepared from more caudal parts of the developing neuroaxis generated fewer neurons compared to the more rostral regions. The only neuronal phenotype identified in these cultures was GABA, with 15–60% of the neurons immunopositive for this neurotransmitter. Thus there appears to be important differences between hENPs dependent on region of origin and time in vitro under standard culture conditions, forming decreasing numbers of neurons with increasing time in culture and more caudal sites of harvest, and with the major identifiable neurotransmitter being GABA. Such characterisation is important in the process of learning how to manipulate the neuronal phenotype of these cells.

High density endocardial mapping of shifts in the site of earliest depolarization during sinus rhythm and sinus tachycardia.

Previous mapping studies of sinus rhythm suggest faster rates arise from more cranial sites within the lateral right atrium. In the intact, beating heart, mapping has been limited to epicardial plaques or single endocardial catheters. The present study was designed to examine shifts in the site of the earliest endocardial depolarization during sinus rhythm and sinus tachycardia using high density activation mapping. Noncontact mapping of the right atrium during sinus rhythm was performed on ten anesthetized swine. Recordings were made during sinus rhythm, phenylephrine infusion, and isoproterenol infusion. The hearts were then excised and the histological sinus node identified. The mean minimum and maximum cycle lengths recorded were 355 +/- 43 and 717 +/- 108 ms. A median of three (range two to five) sites of earliest endocardial depolarization were documented in each animal. With increasing heart rate the site of earliest endocardial depolarization remained stationary until a sudden shift in a cranial or caudal direction, often to sites beyond the histological sinoatrial node. The endocardial shift was unpredictable with considerable variation between animals; however, faster rates arose from more cranial sites (r = 0.46, P = 0.023). There was no difference in the mean cycle length of sinus rhythm originating from specific positions on the terminal crest (r = 0.44, P = 0.17). Cranial sites displayed a more diffuse pattern of early depolarization than caudal sites. In the porcine heart the relationship between heart rate and site of earliest endocardial depolarization shows considerable variation between individual animals. These findings may have implications for clinical mapping and ablation procedures.