Adolescent Pigs Research Articles

The Transfer of Disc Pressure to Adjacent Discs in Discography

In vivo experimental study. The primary objective of the study was to investigate pressure transmission to adjacent discs during discography. A secondary objective was to quantify the transmitted pressure, both in contrast injected and noninjected porcine intervertebral discs. Discography is used to before surgery identify painful discs. A pain response during discography that is concordant with the patient's experienced back pain is regarded as an indication that the injected disc is the source of pain. However, the sensitivity and specificity of discography are matters of debate. Pressure-controlled discographies have been reported to reduce the number of false-positive discs using low pressure criteria. Preliminary data indicated a transfer of pressure from an injected to an adjacent disc during discography. Pressure transmission in vivo during lumbar discography, not reported before might, if clinically present, contribute to a false-positive diagnosis. Thirty-six lumbar discs in 9 adolescent pigs were investigated. Intradiscal pressure was recorded during contrast injection, using a 0.36/0.25 mm fiber-optic pressure transducer inserted into the nucleus pulposus via a 22 G needle. The pressure was measured simultaneously in 2 adjacent discs during contrast injection into 1 of the discs at pressures up to 8 bar. Transmitted pressure was recorded both in noninjected discs and in discs that were prefilled with contrast. Thirty-three discs were successfully examined. During contrast injection, there was an intradiscal pressure rise in the adjacent disc with a median value of 16.0% (range, 3.2-37.0) over baseline pressure. There was no significant difference in pressure increase between the noninjected and prefilled discs (P < 0.68). Discography of porcine discs induces a pressure increase in adjacent discs. A similar pressure transfer during human clinical discography might elicit false-positive pain reactions.

Cardiovascular responses to prolonged carbon dioxide pneumoperitoneum in neonatal versus adolescent pigs

Long-lasting minimally invasive procedures are increasingly used for children. However, the hemodynamic effects of a prolonged carbon dioxide (CO(2)) pneumoperitoneum (PP) on small infants are poorly understood and may differ from the effects on adolescents. This study aimed to detect and compare these effects in neonatal and adolescent pigs. Six neonatal pigs weighing 5.6-6.4 kg and six adolescent pigs weighing 51-57 kg underwent a prolonged CO(2) PP of 180 min. Five neonatal pigs weighing 5.7-6.6 kg underwent sham PP as an additional control group. All the animals received crystalloid electrolyte solution at 10 ml/kg/h during the experiments. After CO(2) decompression, all the animals were monitored for a further 120 min. The end points of the study were mean arterial pressure (MAP), central venous pressure (CVP), and cardiac index (CI). The parameters were assessed after a 60-min resting phase (i.e., after initial placement of catheters in the jugular vein, the carotid artery, and the femoral artery four times during CO(2) PP and three times afterward. The comparison of neonates and adolescent pigs showed that neonates had a significantly more pronounced decrease in MAP during CO(2) PP (88.1 +/- 2.7% of baseline vs 95.1 +/- 1.6%; p < 0.05) and the recovery period (71 +/- 5.1% vs 86.4 +/- 1.4%; p < 0.05). Differences in CVP changes between the neonatal and adolescent pigs during and after CO(2) PP were not significant. For the neonates, the decrease in CI was most pronounced during the recovery period after decompression of the CO(2) PP and significantly less than in adolescents (84.3 +/- 3.3% of baseline vs 97.4 +/- 4.5%; p < 0.05). The neonates with sham PP did not show any significant MAP, CVP, or CI changes during the experiments. A prolonged CO(2) PP induces hypotension and cardiac depression in neonatal but not in adolescent pigs. Thus, intensive monitoring during prolonged laparoscopic procedures and particularly afterward may be mandatory for neonates.

Bulging of the Inner and Outer Annulus During In Vivo Axial Loading of Normal and Degenerated Discs

Comparison of in vivo biomechanical outcomes between experimental and control group animals. To quantify the in vivo bulging response of the inner and outer annulus in animals with and without disc degeneration. Prior attempts to quantify the load-deformation response of the inner annulus have most often relied on in vitro preparations. Unfortunately, to visualize the inner annulus, these in vitro approaches rely on disc modifications that may result in nonphysiologic behaviors. In response to this problem, in vivo techniques were developed to quantify regional bulging of the inner and outer annulus during applied axial loading. Two groups of pigs were tested: a normal group and a group having disc degeneration that was induced surgically 3 months earlier. Eight adolescent pigs were evaluated and for each animal, a miniature servohydraulic actuator was attached to the third and fourth lumbar vertebrae to deliver a cyclic axial loading protocol (300 N, 1 Hz, 10 cycles) whereas regional deformations of the annulus were visualized ultrasonically via retroperitoneal access. For the normal animals, image analysis demonstrated a significantly greater bulging of the inner annular region when compared with the outer annular region. In animals with disc degeneration, the inner and outer annular regions were equal in their bulging response, which ranged from 0 bulging to 37% greater than the average response of the normal animals. This work supports prior in vitro studies that observed maximal disc bulging in the inner annulus and minimal bulging in the external annulus. Results for this in vivo study suggest that this normal bulging gradient is lost with degenerative disc disease. Compared with in vitro approaches, this new in vivo technique has the potential to demonstrate disc behavior in a variety of loading conditions and/or with a variety of induced disc pathologies.

Ontogenic changes of the control by phosphodiesterase‐3 and ‐4 of 5‐HT responses in porcine heart and relevance to human atrial 5‐HT4 receptors

Atrial inotropic responses to 5-HT mediated through 5-HT(4) receptors fade, presumably through phosphodiesterase (PDE) activity. We investigated the influence of a selective inhibitor of PDE3 (cilostamide) or of PDE4 (rolipram) on the fade of 5-HT responses in atrial muscle. 5-HT responses were compared, ex vivo, on sinoatrial beating rate of newborn piglets, porcine atrial and ventricular force, and human atrial force. cAMP levels were assessed in piglet atrium. 5-HT-evoked sinoatrial tachycardia did not fade and was not potentiated by cilostamide (300 nmol.L(-1)) or rolipram (1 micromol.L(-1)). Inotropic responses to 5-HT faded in atria from piglets, adolescent pigs and humans. Cilostamide reduced atrial fade of 5-HT responses in adolescent pigs and humans but not in newborn piglets. Cilostamide disclosed 5-HT ventricular responses in newborn, but not adolescent pigs. Rolipram reduced fade of atrial 5-HT responses in newborn and adolescent pigs but not in humans. Concurrent cilostamide + rolipram abolished fade of 5-HT responses in porcine left atria and facilitated ventricular 5-HT responses, but did not reduce residual fade in human atrium in the presence of cilostamide. 5-HT-evoked increases in cAMP faded; fade was abolished by concurrent cilostamide + rolipram. PDE3-induced control of porcine 5-HT responses differed in atrium and ventricle and changed with age. PDE3 and PDE4 jointly prevented fade of inotropic and cAMP responses to 5-HT in porcine atrium. Unlike porcine atria, only PDE3 induced fade of 5-HT responses in human atria.

Evaluation of Complete and Partially Obstructed Kidneys Using Gd-DTPA Enhanced Dynamic MRI in Adolescent Swine

Aim of this study was to evaluate the dynamic changes in renal relative signal intensity (RSI) following the administration of Gd-DTPA in adolescent pigs with complete and partial unilateral ureteric obstruction. Pigs were divided into 3 groups: partial and complete unilateral ureteric obstruction and controls. Complete unilateral ureteric obstruction (CUUO) was created by ligating the left ureter, whereas partial unilateral ureteric obstruction (PUUO) was created in pigs of 2 weeks of age by embedding the left ureter into the psoas muscle. Dynamic MRI was performed before and at 0 - 60 min after an intravenous bolus injection of Gd-DTPA. Mean RSI of the renal cortex, medulla and pelvis was measured and interpreted as an indirect measure of the renal function. In addition, renography was performed, and renal morphology was examined IN VITRO. Three phases of RSI were identified. The dynamic RSI patterns differed markedly between obstructed and control kidneys. In PUUO kidneys, Phase 1 of the mean RSI of the cortex and medulla demonstrated a decreased amplitude and prolonged duration, whereas in Phase 2 the mean RSI of the pelvis was increased. In acute CUUO kidneys, the mean RSI patterns were similar to those of controls, except for a significant increase of the pelvic mean RSI. Gd-DTPA enhanced dynamic MRI allowed a characterization and differentiation of renal function and morphology of normal and obstructed kidneys, and secondly, provided potentially important information on renal concentrative and filtration availability.

Age-related changes in the neuromuscular development of the internal anal sphincter

Purpose The internal anal sphincter (IAS) plays an important role in the pathophysiology of constipation and incontinence. We hypothesized that functional bowel obstruction in premature infants is because of a poorly developed IAS. We investigated the neuromuscular development of IAS in fetal, newborn, and adolescent pigs. Methods Paraffin sections of IAS from 5 different age groups, E60, E90, 1 day, 4, and 12 weeks old, were stained with protein gene product 9.5 (PGP9.5), α-smooth muscle actin ( α-SMA), caldesmon (CALD), calponin (CALP), and desmin (DES) antibodies. Quantification of results was performed by grading the density of immunostaining. Results The PGP9.5-positive ganglion cells were observed in the myenteric and submucosal region of the entire length of the IAS at E60. An increase in ganglion cell size and density was observed with increasing age. There were striking differences in the density of PGP9.5, α-SMA, DES, CALD, and CALP immunoreactive fibers between prenatal and postnatal period with gradient increase in the number of fibers from after birth to 12 weeks of age. Conclusion This study shows for the first time that there are age-related differences in the distribution of neurons and smooth muscle cell components in the IAS. The decreased expression of contractile and cytoskeleton proteins in smooth muscle cells together with decreased expression of neurons in the IAS in the perinatal period may lead to motility dysfunction causing functional intestinal obstruction seen in premature infants.

Intradiscal pressure in the degenerated porcine intervertebral disc

Measuring intradiscal pressure is one way of mechanically assessing the discs degenerative state. In this study, the load-bearing capacity of degenerated and their adjacent lumbar intervertebral discs was evaluated using two different injury models. Seventeen adolescent pigs were divided into two groups, an annulus injury group and an endplate injury group. The annulus injury group was subjected to a stab incision in the L3-L4 disc, whereas the endplate injury group received a cranial endplate perforation of the L4 vertebral body. Both groups were biomechanically evaluated three months later using a miniaturized servohydraulic testing machine across L2-L4 and with two pressure needles inserted into the nucleus pulposus of the L2-L3 and L3-L4 discs. Linear relationships between the intradiscal pressure and the applied load were determined within the load range studied. When comparing the ratio of the injured to the adjacent disc pressure, the endplate injury was lower (mean value 0.31) than the annulus injury (mean value 0.51). The pressures in the discs adjacent to the degenerated level were found to be slightly higher. This increase can be expected due to a redistribution in mobility demands in segments adjacent to those with increased stiffness, i.e. degenerated intervertebral discs.

Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells

Maturation of fetal alveolar type II epithelial cells in utero is characterized by specific changes to lung surfactant phospholipids. Here, we quantified the effects of hormonal differentiation in vitro on the molecular specificity of cellular and secreted phospholipids from human fetal type II epithelial cells using electrospray ionization mass spectrometry. Differentiation, assessed by morphology and changes in gene expression, was accompanied by restricted and specific modifications to cell phospholipids, principally enrichments of shorter chain species of phosphatidylcholine (PC) and phosphatidylinositol, that were not observed in fetal lung fibroblasts. Treatment of differentiated epithelial cells with secretagogues stimulated the secretion of functional surfactant-containing surfactant proteins B and C (SP-B and SP-C). Secreted material was further enriched in this same set of phospholipid species but was characterized by increased contents of short-chain monounsaturated and disaturated species other than dipalmitoyl PC (PC16:0/16:0), principally palmitoylmyristoyl PC (PC16:0/14:0) and palmitoylpalmitoleoyl PC (PC16:0/16:1). Mixtures of these PC molecular species, phosphatidylglycerol, and SP-B and SP-C were functionally active and rapidly generated low surface tension on compression in a pulsating bubble surfactometer. These results suggest that hormonally differentiated human fetal type II cells do not select the molecular composition of surfactant phospholipid on the basis of saturation but, more likely, on the basis of acyl chain length.

Fracture Patterns of the Adolescent Porcine Spine: An Experimental Loading Study in Bending-Compression

To expose functional spinal units from adolescent porcine to mechanical flexion-compression and extension-compression to failure. The biomechanical, radiologic, magnetic resonance imaging, and histologic characteristics are described. The aim of the present study was to investigate the fracture pattern of functional spinal units from adolescent porcine lumbar spines in in vitro compression loading and bending. In several studies, it has been shown that the adolescent spine, especially the vertebral growth zones, is vulnerable to trauma. A high frequency of abnormalities affecting the spine has been found among athletes participating in sports with high demands on the back. The etiology of these abnormalities is still a controversial issue. Sixteen functional spinal units obtained from eight adolescent male pigs were used. Eight functional spinal units were exposed to flexion-compression and eight functional spinal units to extension-compression loading to failure. They were examined with plain radiography and magnetic resonance imaging before and after the loading. The functional spinal units were finally examined macroscopically and histologically. Fractures/separations were seen in the growth zone anteriorly and more frequently, posteriorly in functional spinal units exposed to flexion-compression. In the extension-compression group, such injuries occurred only anteriorly. Only large fractures could be seen on plain radiographs and on magnetic resonance imaging. Macroscopically, a fracture/separation could be seen in 15 cases and histologically in all 16 cases. The median angle at failure for the flexion group was 17 degrees (range, 12-19) and for the extension group 17 degrees (range, 13-19 degrees). The median ultimate compression load in the flexion-compression group was 1894 N (range, 1607-3138 N) and in the extension-compression group 1801 N (range, 1158-2368 N). The weakest part of the growing porcine lumbar spine, when compressed into flexion- or extension-compression, was the growth zone. The injury was more extensive in extension loading than during flexion loading. Growth zone injuries of the adolescent spine may go undetected on plain radiographs and magnetic resonance imaging.

Quantification of lung water by transpulmonary thermodilution in normal and edematous lung

Purpose: To analyze the accuracy of the transpulmonary thermodilution method in the determination of extravascular lung water (EVLW). Material and Methods: Acute lung injury was produced in eight adolescent pigs weighing 28 to 35 kg by bronchoalveolar lung lavage. EVLW was measured by transpulmonary thermodilution method before and after the intratracheal introduction of 250 or 500 mL of saline solution in different lung injury conditions. No corrections for anatomic dead space were made. Results: When 250 mL was introduced, 195 ± 17 mL was detected in normal (uninjured) lungs versus 74 ± 57 mL in edematous (injured) lungs ( P < .05). When 500 mL was introduced, 343 ± 67 mL was detected in normal lungs versus 160 ± 51 mL in edematous lungs ( P < .001). Considering all determinations together, there was a very high negative correlation between the baseline EVLW and the percentage of EVLW detected (r = -0.92, P < .001). Conclusion: The transpulmonary thermodilution method is very accurate to detect changes in EVLW in normal lungs. In edematous lung, this method may underestimate the EVLW.

A porcine astrocyte/endothelial cell co-culture model of the blood–brain barrier

A method for the isolation of porcine atrocytes as a simple extension of a previously described procedure for isolation of brain capillary endothelial cells from adolescent pigs [Methods Cell Sci. 17 (1995) 2] is described. The obtained astroglial culture purified through two passages and by the method of the selective detachment was validated by a phase contrast microscopy and through an immunofluorescent assay for the glial fibrillary acidic protein (GFAP). Porcine astrocytes were co-cultivated with porcine brain capillary endothelial cells (PBCEC) for the development of an in vitro blood–brain barrier (BBB) model. The model was visualized by an electron microscopy and showed elevated transendothellial electrical resistance and reduced inulin permeability. To our knowledge, this is the first report for the establishment of a porcine astrocyte/endothelial cell co-culture BBB model, which avoids interspecies and age differences between the two cell types, usually encountered in the other reported co-culture BBB models. Considering the availability of the porcine brain tissue and the close physiological and anatomical relation between the human and pig brain, the porcine astrocyte/endothelial cell co-culture system can serve as a reliable and easily reproducible model for different in vitro BBB studies.

Tissue engineering of arteries by directed remodeling of intact arterial segments.

Traditional approaches to generating tissue-engineered arteries in vitro rely on expansion of cells in culture to seed appropriate scaffolds. In most envisioned applications, small autologous blood vessels would be harvested and used as a source for these cells. We propose that small autologous arteries, not the cells derived from them, may be an attractive starting point for engineered arteries. This approach capitalizes on the ability of intact arteries to grow and remodel in response to chronic changes in their mechanical environment. Carotid arteries from juvenile (approximately 30-kg) pigs were stretched longitudinally in an ex vivo perfusion system over 9 days. This resulted in a 40% increase in artery length at physiological longitudinal stress and a 20 +/- 3% increase when unstressed. Control arteries were perfused for 9 days ex vivo at their physiological loaded length. Control and elongated arteries displayed native appearance (macroscopic and histological), excellent viability (cellularity and mitochondrial activity), normal vasoactivity, and similar mechanical properties (ultimate stress and ultimate strain) as compared with freshly harvested arteries. Growth, as opposed to just redistribution of existing mass, contributed to elongation as evidenced by an increase in artery weight. Results on elongation of arteries from neonatal and adolescent pigs are also presented and discussed.

Postnatal neurogenesis in the vasopressin and oxytocin-containing nucleus of the pig hypothalamus

The vasopressin and oxytocin-containing nucleus (VON) of the pig hypothalamus demonstrates dramatic postnatal growth in nucleus size, both volume and neuron number, during puberty, and continues to increase in size in the adult sexually mature female pig throughout its reproductive prime. This study was designed to show that postnatal neurogenesis is responsible for the VON growth that occurs between adolescence and maturity. Recently divided neurosecretory cells of the hypothalamus were identified in adolescent and mature non-lactating female pigs using a sequential immunohistochemistry double-labeling technique with monoclonal mouse antibodies to detect vasopressin and proliferating cell nuclear antigen (PCNA), a protein associated with the S phase of the cell cycle. A computer-assisted image-analysis system was used to assess nucleus volume and neuron counts. The VON of the mature dry sows was significantly larger in volume and number of vasopressin neurons than the VON of the adolescent pigs. Double-labeled cells were noted in the VON of both adolescent and mature dry sows, but the number and proportion of double-labeled cells was significantly higher in adolescent pigs. Our results indicate the presence of neurons containing PCNA in the VON of the pig hypothalamus. This suggests that mitosis of neurogenic precursors plays a role in the growth of the nucleus.

Mechanical environment, donor age, and presence of endothelium interact to modulate porcine artery viability ex vivo.

Though ex vivo culture of arteries is a widely used model of native arteries and is closely aligned with efforts to generate tissue-engineered arteries, the effects of culture conditions on artery viability are poorly characterized. To investigate factors regulating long-term viability of cultured arteries, carotid arteries from neonatal and adolescent pigs were perfused for up to 27 days with steady laminar flow ranging from approximately 2% to approximately 200% of physiological flow rates. Arteries from neonatal animals (2 weeks old, approximately 5 kg) were susceptible to spontaneous progressive endothelial denudation followed by deterioration of the vessel wall that spread from luminal to abluminal regions. Subphysiological levels of flow and pressure abrogated this deterioration. Arteries harvested from adolescent (6 months old, approximately 100 kg) animals maintained viability and retained structure for at least 9 days as assessed by normal histology, presence of intact endothelium, normal mitochondrial activity, and low levels of cell death and proliferation, unless the vessels were subjected to superphysiological levels of flow or the endothelium was intentionally denuded. Adolescent arteries perfused at subphysiological, but not physiological, flow rates maintained viability and normal structure for at least 27 days. These data indicate that under the appropriate conditions, arteries may be cultured long term but careful attention to the viability is merited.

Brain Excitatory Amino Acid Concentrations Are Lower in the Neonatal Pig: A Buffer against Excitotoxicity?

Hypoglycemic brain damage has been associated with high levels of the excitatory amino acids (EAA) aspartate and glutamate in the newborn and adult. We hypothesized that newborn piglet EAA would be different from those of older pigs when stressed with severe insulin-induced hypoglycemia (<30 mg/dl). Brain EAA were measured in piglets and adolescent pigs via microdialysis. Eleven of 12 newborn normoglycemic piglets had no detectable baseline levels (<0.5 µM) of EAA, while pigs had aspartate and glutamate concentrations of 1.78 ± 0.44 and 3.43 ± 1.14 µM (mean ± SEM), respectively. Piglet aspartate and glutamate concentrations reached but did not significantly exceed normoglycemic pig levels after 2 h with plasma glucose values ≤20 mg/ml. Elevations in EAA were only detected in piglets whose EEG activity ceased. Aspartate and glutamate concentrations did not increase in insulin-treated pigs nor in control animals. We speculate that newborns with blood glucose less than clinically acceptable values (35 mg/dl) may be protected from EAA-associated neuronal damage during acute hypoglycemia. Lower normoglycemic and hypoglycemic levels of EAA in newborns when compared to older pigs provide this protection.

Sacroiliac Joint Involvement in Activation of the Porcine Spinal and Gluteal Musculature

In the search for causes of low back pain, the sacroiliac joint has gained renewed interest as a possible pain generator. There is reason to believe that the sacroiliac joint plays a regulatory role involving reflex muscle activation, which controls trunk mobility and stability, as well as locomotion. The aim of this experimental study was to determine whether stimulation of nerves in the sacroiliac joint and joint capsule could elicit contractions in porcine gluteal or lumbar spinal muscles. Via a lateral retroperitoneal approach and using hypodermic needles, bipolar stimulating wire electrodes were inserted into the ventral area of the sacroiliac joint and directly under the surface of the capsular membrane, in 10 adolescent pigs (45 kg). This procedure was performed bilaterally, thus establishing two bilateral stimulation sites in the joints. Six electromyographic electrodes were unilaterally inserted into the following muscles: multifidus, gluteus medius, gluteus maximus, and quadratus lumborum. On stimulation within the ventral area of the joint, predominant responses occurred in both the gluteus maximus and quadratus lumborum muscles. However, when stimulating the capsule, the greatest muscular responses were detected in the multifidus muscles. This study addressed the possible regulatory function of the sacroiliac joint, namely, its involvement in activation of the spinal and gluteal muscles, which help control locomotion and body posture, as well as provide stability on the segmental level in the lumbar spine.

Interaction between the porcine lumbar intervertebral disc, zygapophysial joints, and paraspinal muscles.

A porcine model was used to study whether muscular activation in the paraspinal muscles caused by nerve stimulation in the anulus fibrosus of a lumbar intervertebral disc could be altered by saline injection into the zygapophysial (facet) joint. To elucidate possible mechanisms regarding the nerve pathways and interactions between the intervertebral disc, zygapophysial joints, and the paraspinal musculature. The physiologic basis for chronic low back pain, including muscular spasm, is uncertain. Although extensive research involving the lumbar motion segments and the surrounding tissues has been performed, the neuromuscular connection has not been sufficiently investigated. Twenty-three adolescent pigs were used to measure the electromyographic response in the paraspinal musculature to electrical stimulation of the posterolateral L3-L4 anulus fibrosus, before and after introduction of physiologic saline into the zygapophysial joint. Motor unit action potentials were recorded using three sets of needle electrodes placed into the deepest fascicles of the multifidus, bilateral to the L4 and L5 spinous processes, and into the central longissimus musculature, bilateral to the L4 spinous process. Stimulation of the nerves within the posterolateral anulus of the disc elicited reactions in the paraspinal muscles, namely the lumbar multifidus and longissimus. Introduction of physiologic saline into the zygapophysial joint resulted in a reduction in the motor unit action potential amplitude. This reduction was manifested as an immediate and constant reduction, a graded reduction, or a delayed reaction, during which the reduction occurred an average of 5 minutes after the saline injection. Introduction of physiologic saline into the zygapophysial joint reduced the stimulation pathway from the intervertebral disc to the paraspinal musculature. The zygapophysial joints may therefore have a regulating function, controlling the intricate neuromuscular balance in the lumbar motion segment.

Role of Ischemic Gradient in Neovascularization of Interpolated Skin Flaps

To investigate the significance of the ischemic gradient between interpolated skin flaps and the recipient bed and to determine its role in flap viability. Bilateral interpolated skin flaps were elevated in 10 pigs and intravenous fluorescein was used to define a border of pedicle perfusion. Flaps were assigned to 1 of 2 groups: proximal flaps, which were contained within the fluorescein border, or distal flaps, which extended 3 cm beyond the fluorescein border. Flaps were then transferred to an adjacent cutaneous defect and pedicles were divided after 2 weeks. The flap and pedicle portions were evaluated separately and viability was quantified. Ten adolescent pigs with bilateral flaps. None were withdrawn. Intravenous fluorescein (20 mg/kg) to determine extent of perfusion in the flaps. Proximal flaps (n = 10) maintained excellent viability with the pedicles attached. After pedicle division, however, partial flap and pedicle necrosis developed. Distal flaps (n = 10) promptly showed signs of ischemia and congestion but soon showed improved vascularity. A statistically significant improvement was seen in mean percent viability of the distal group compared with the proximal group (P < .05) (Student t test). The more ischemic flap-pedicle complex resulted in greater viability after pedicle division. The ischemic gradient seemed to represent a potent angiogenic stimulus to the recipient bed.

Intraneuronal β-amyloid immunoreactivity in the CNS

The high degree of overlap in the neuropathology outcome of Alzheimer's disease (AD), Down's Syndrome (DS), and coronary heart disease suggest a possible interrelationship. The pattern of hippocampal and cortical intraneuronal βA4 immunoreactivity is strikingly similar in AD, DS, coronary heart disease, and two separate animal models of coronary heart disease. Cells in fascia dentata and large cortical neurons were βA4 immunedecorated in half the AD and DS subjects studied. Similar neuronal staining occurred in half the age-matched coronary heart disease subjects, but was absent in each nonheart disease control investigated. Analogous accumulations of neuronal βA4 immunoreactivity were induced in rabbit brain by dietary administration of high cholesterol, and this effect could be reversed by regression of the experimental diet. Decreased density ( p < 0.05) and cellular staining intensity occurred after 2 weeks of control diet following 8 weeks of high cholesterol. Microgliosis accompanied the accumulation of βA4 immunoreactivity in the cholesterol-fed rabbits and persisted after regression of the diet and decreases in neuronal βA4 immunoreactivity. An identical pattern of neuronal βA4 immunoreactivity was induced in the brains of adolescent pigs after acute ligation of the left anterior descending coronary artery (LAD) compared to surgical and anesthetic controls. The mean number of βA4 immunoreactive neurons was significantly increased ( p < 0.05) in the cortex and hippocampus of pigs with a ligated LAD compared to both control groups. Increased density and intensity of neuronal βA4 immunoreactivity induced by ligation of the LAD was commensurate with the severity of the decreased cardiac output in the LAD group, but not in the anesthetic control groups with decreased cardiac output. The incidence of ALZ-50 (A68) immunoreactive neurons also increased in the ligated pigs compared to both control groups. The data suggest a neuronal origin of βA4 immunoreactive peptide(s), which can be cleared from the brain by microglia after severe accumulation is induced. This could indicate that reduced clearance of β-APP metabolic by-products could contribute to a metabolic backlog and redirection of peptide processing by microglia to extracellular deposition. Neuronal accumulation of βA4 immunoreactivity could be due to the effect of circulating factors on brain function in both animals models. It is likely that animal models of coronary heart disease may be useful in disclosing the mechanism of SP formation and induction of ALZ-50 immunoreactivity irrespective of their pathoclinical significance.

Latency of the jaw-opening reflex in the premature, preweaning and adolescent pig (hanford strain miniature pig, Sus scrofa)

The jaw-opening (digastric) reflex was elicited by electrical stimulation of oral mucosa in miniature pigs ( Sus scrofa) varying in age from 5 days premature to 101 days post-term. The latency of reflex electromyographic activity varied between 12–14 ms in the most immature animals and 9–11 ms in the oldest animals. The very long-latency digastric responses found in the immature young of nesting mammals were not seen in the relatively precocious young of this species.