Developmental changes in heart rate variability during exposure to prolonged hypercapnia in piglets.

The hypothesis that hypercapnia-induced differences in heart rate variability (HRV) would emerge during early maturation was tested using a developing porcine model. Piglets were randomly assigned to either exposed (10% CO2 for 1 h) or control (100% O2) conditions, and then to one of three study groups: (a) 5-8 days old, (b) 13-15 days old, (c) 26-34 days old. Experiments were performed on pairs of age-and litter-matched animals that were anesthetized, paralyzed, and artificially ventilated.

Baroreceptor-related dysrhythmias in piglets with selective autonomic denervation of the heart.

This study was carried out to determine whether selective cardiac autonomic denervation performed on neonatal swine would evoke dysrhythmias later in development. Piglets (n = 27; 5-10 days old) underwent unilateral stellate ganglion ablation, or right cardiac vagotomy, or sham surgery. Fifty to sixty days after denervation, acute experiments were performed to evaluate responses to baroreceptor activation.

Electrocardiographic changes during postnatal development in conscious swine with cardiac autonomic imbalance.

Using a conscious swine model, we studied the effects of different patterns of cardiac autonomic denervation on alterations of R-R and Q T intervals for 8 postnatal weeks. Newborn pigs were assigned randomly to four different groups: sham-operated controls (C), stellate ganglion ablation (SGX), either left (LSGX) or right (RSGX), and the right cardiac vagus nerve (RCVX) transection. The ECGs were recorded by telemetry while animals rested quietly or were judged behaviorally to be asleep.

Rhythmicities in sympathetic discharge: a signal of cardiorespiratory integration in developing animals.

We have been pursuing various avenues of investigation to elucidate the postnatal maturation of neural regulation of cardiovascular and respiratory integration. In this paper we present our results from a systematic analysis of age-related modulations of sympathetic (SYMP) activity with respect to experimental alterations in baroreceptor afferent inputs. The three age groups of piglets were chosen based on different responses to a complex stimulus, i.

Changes in R-R and Q-T intervals following cardiac vagotomy in neonatal swine.

Asymmetric innervation of the myocardium, especially a predominance of sympathetic innervation, may establish conditions whereby electrical instability could result. Using a swine animal model, we studied the effect of right cardiac vagal denervation on the variability of R-R and Q-T intervals. Newborn pigs were assigned randomly to two groups: sham-operated controls (C), or denervation of the right cardiac vagus nerve (RCVX).

CO(2)-induced expression of c-fos in the nucleus of the solitary tract and the area postrema of developing swine.

This investigation was performed to determine whether hypercapnic exposure elicited expression of the c-fos protooncogene product, FOS, in nucleus of the solitary tract (NTS) and area postrema (AP) neurons of developing swine. Mean arterial blood pressure (MAP) and heart rate (HR) were also monitored to evaluate whether numbers of neurons containing FOS were related to changes of MAP and HR. In each experiment, two litter-matched piglets were prepared simultaneously, i.

The area postrema of newborn swine is activated by hypercapnia: relevance to sudden infant death syndrome?

This study was performed to investigate a role of the neonatal area postrema (AP) in the chemoreceptor response to hypercapnia which is defective in sudden infant death syndrome (SIDS). AP responses to CO2 inhalation were monitored in 1 to 5 week old piglets by mapping neurons that were induced to express the c-fos gene product, Fos--a marker of functional activation. Interpretive confounds were minimized by controlling for hypoxia, the effects of surgical procedures and ambient environmental stressors on neuronal activity (c-fos expression).

Presence of a non-NMDA glutamate receptor subtype in the sympathetic nervous system of neonatal swine.

For the first time, the GluR-1 subtype of AMPA receptor was identified in the sympathetic nervous system of neonatal swine, an animal model of human development and heart disease. The rationale was to seek evidence of a role ascribed to glutamate in cardiorespiratory regulation in the laboratory rat. The receptor was demonstrated with the avidin-biotin immunoperoxidase technique by using an affinity-purified polyclonal antibody judged to be specific to Glu-R1 in several species.

Emergence of lung-inflation-related sympathetic nerve activity in spinal cord transected neonatal swine.

Sympathetic (SYMP) nerve activity in spinal intact neonatal swine is comprised of prominent bursts reflecting modulation by supraspinal structures involved in shaping central respiratory and baroreceptor activity. After spinal cord transection (SCT), we found no evidence of such modulation. SYMP activity was now related to the ventilatory cycle, exhibiting bursts only during lung inflation.

Induction of c-fos gene expression by spinal cord transection in the rat.

Sympathetic nerve activity is maintained after high spinal injury through circuits that remain in question. We evaluated patterns of c-fos gene induction as a monitor of spinal neurons responding to high spinal cord transection in the rat. Rats were anesthetized with isofluorane.

Preliminary evidence for the evolution in complexity of heart rate dynamics during autonomic maturation in neonatal swine.

Previous studies suggest that the autonomic nervous system plays an important role in the generation of complex heart rate dynamics. Therefore, we hypothesized that the complexity (irregularity) of cardiac interbeat intervals would evolve with the maturation of autonomic innervation to the heart. Twelve healthy newborn piglets were implanted with ECG transmitters and studied at one or more different ages up to 33 days of age, the period during which pigs develop functional sympathetic innervation of the heart from the stellate ganglia.

Induction of c-fos gene expression by spinal cord transection in Sus scrofa.

Functional responses of primary sensory afferents and spinal cord were monitored in swine subjected to a high cervical (C1) spinal transection. Two and a half hours after transection, dorsal root ganglia and cervical and thoracolumbar spinal segments were processed immunocytochemically for the c-fos gene product, Fos and related antigens. In spinal-transected animals, Fos-like immunoreactivity (FLI) was induced in spinal laminae I, V, VII and X and the intermediolateral cell column but not in sensory ganglia as compared to controls: spinal-intact age-matched littermates.

Effects of cardiac autonomic imbalance on postnatal changes in the electrocardiographic Q-T interval in conscious swine.

The effects of partial autonomic denervation of the heart rate and Q--T interval were examined during maturation in swine. Four groups of newborns were prepared: right stellate ganglionectomy (RSG), left stellate ganglionectomy (LSG), right cardiac vagotomy (RCV) and sham-operated. Swine were studied postsurgically for eight weeks.

Anatomy of medullary and peripheral autonomic neurons innervating the neonatal porcine heart.

Gross and microscopic anatomical investigations were carried out in 14 piglets aged from 4 to 66 days. True Blue (7-50 microliters) and Diamidino Yellow (7-50 microliters) were injected individually into 2 different cardiac sites (the right atrial ganglionated plexus, the inferior vena cava, inferior atrial ganglionated plexus, the right atrium or the right ventricle). Gross anatomy: Globular superior cervical and nodose ganglia, elongated stellate ganglia, multiple small middle cervical ganglia and multiple small mediastinal ganglia along the course of cardiopulmonary nerves were identified.

Age-related effects of cardiac sympathetic denervation on the responses to cardiopulmonary receptor stimulation in piglets.

The effects of right stellate ganglionectomy (RSG) and bilateral stellate ganglionectomy (BSG) on cardiovascular responses to phenyl biguanide (PBG, 80 micrograms/kg) were studied in 1- and 8-wk-old piglets. Animals were anesthetized with Saffan, paralyzed, thoractomized, and ventilated with 100% O2. Recordings of the ECG (lead II) and aortic pressure (AoP) were used to compute the maximum R-R interval, heart rate (HR), and mean AoP, and to determine the occurrence of atrioventricular conduction block (AVB).

Hypotension-induced expression of the c-fos gene in the medulla oblongata of piglets.

Neural networks that mediate the reflex response to baroreceptor withdrawal were explored in Sus scrofa. Induction of c-fos was used as a monitor of synaptic activity in response to hypotension sustained by systemic administration of a peripheral vasodilator, sodium nitroprusside. Patterns of c-fos gene expression were compared between Saffan-anesthetized experimental animals and age-matched normotensive controls administered vehicle.

Postganglionic sympathetic discharge in neonatal swine.

We hypothesized that cardiac and respiratory modulation of postganglionic peroneal activity appeared in an age-related manner. In anesthetized, paralyzed and artificially ventilated piglets, simultaneous recordings of efferent phrenic and peroneal discharges were obtained during hyperoxia (fraction of inspired oxygen, FiO2 = 1.0) and hypoxia (FiO2 = 0.

The presence of coherence in sympathetic and phrenic activities in a developing mammal.

To determine whether are development changes in the baroreceptor and central respiratory modulation of sympathetic activity, we used ordinary and partial coherence spectral analyses on cervical and splanchnic sympathetic activity in swine 1-36 days old. Removal of baroreceptor influences from cervical sympathetic and splanchnic spectra using partialization shows that 3-6 Hz peaks are due to baroreceptors since coherence decreased in > 19 days old while remaining unchanged in < 2 weeks old piglets. The 8-12 Hz band (present in normal coherence after 21 days) was revealed in piglets < 14 days old after removal of respiratory modulation by partialization; similarly increased coherence was also observed in the 16-18 Hz band through 3 weeks.

Development of a swine animal model for the study of sudden infant death syndrome.

An animal model with selective cardiac autonomic denervation was developed in neonatal swine for the purpose of future studies concerning the possible role of abnormal cardiac innervation in the etiology of sudden infant death syndrome. Twenty-six 4- to 8-day old piglets were randomly assigned to one of the following treatment groups: right stellate ganglionectomy (RSG), left stellate ganglionectomy (LSG), right cardiac vagotomy (RCV), and sham-operated control group. Piglets were anesthetized with Saffan and mechanically ventilated on room air.

NADPH-diaphorase activity in piglet intestinal mucosa.

The distribution of the enzyme synthesizing nitric oxide (NO) has been characterized in several mammalian enteric nervous systems. Two methods, immunohistochemical staining, employing anti-nitric oxide synthase antibodies, and histochemical localization of NADPH-diaphorase (NADPH-D), have given the same results. On the other hand, few studies have investigated nitric oxide synthase (NOS) in the gastrointestinal mucosa.

Neuronal activity of the stellate ganglia in neonatal swine.

In anesthetized, paralyzed, and artificially ventilated neonatal pigs, neuronal activity was recorded extracellularly from the intact right stellate ganglion. Of 301 investigated neurons, only a few had spontaneous activity: 27 neurons generated activity either during lung inflation or deflation, and 1 neuron generated activity related to the cardiac cycle. The remaining 273 neurons were activated by stroking of body hair or by light pressure applied to various somatic sites.

Effects of GABAA receptor antagonism on inspiratory activities in kittens.

In anesthetized kittens (< 1 to 24 days old), the effects of GABAA receptor antagonism on phrenic, hypoglossal and cervical sympathetic discharges were examined by i.v. bicuculline infusions during hyperoxia and hypoxia.

Presumptive adrenergic neurons containing phenylethanolamine N-methyltransferase immunoreactivity in the medulla oblongata of neonatal swine.

Given the importance of the swine (Sus scrofa) as an animal model for human development, physiology and disease, neurons containing the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), were mapped in the medulla oblongata of neonatal swine as a first step in identifying their roles in central autonomic control. Neurons were labeled immunocytochemically by using an antiserum to PNMT raised in rabbits against trypsin-treated enzyme purified from the bovine adrenal gland. The general regional organization of neurons expressing PNMT (-like) immunoreactivity (ir) in the neonatal swine was similar to data obtained in other species and, in some aspects, more closely resembled the pattern observed in the primate brain.