Vascular Infusion Research Articles

GABA-A-mediated gastrin release induced by baclofen in the isolated vascularly perfused rat stomach

In order to investigate the role of peripheral GABA-B receptors, the effects of the putative GABA-B agonist baclofen on immunoreactive gastrin release from an isolated vascularly perfused rat stomach preparation were examined. The vascular infusion of baclofen at graded concentrations induced a dose-dependent increase in gastrin release; this was unaffected by the GABA-B antagonist delta-aminovaleric acid, but was fully prevented by the selective GABA-A antagonist bicuculline as well as by atropine or tetrodotoxin. These results suggest that the stimulant effects of baclofen are mediated by nervous cholinergic structures associated with GABA-A receptors, and indicate that this GABA-B agonist must be regarded as a partial agonist of peripheral GABA-A receptors.

Rapid regulation of D-glucose transport in basolateral membrane of rat jejunum.

D-Glucose transport and D-glucose inhibitable [3H]cytochalasin B binding to jejunal basolateral membrane vesicles were measured to investigate the possible association between changes in transport activity seen in hyperglycemia and density of transporter sites. Comparison was made between hyperglycemic animals, noninfused rats, and a group infused with sorbitol. Vascular infusion of D-glucose produced a rapid increase in D-glucose transport followed by a delayed and smaller increase in [3H]cytochalasin B binding. The Vmax for glucose uptake was increased after only 30 min of glucose infusion and continued to rise up to 6 h. Comparison with noninfused and sorbitol-infused controls showed that 2 h of glucose infusion produced a 3.5-fold increase in the Vmax for D-glucose uptake while D-glucose-inhibitable binding of [3H]cytochalasin B was unaffected. Six hours of hyperglycemia resulted in the further stimulation of glucose transport (4.1-fold) and a significant 1.8-fold increase in cytochalasin B binding over that for noninfused animals. Vesicles prepared from animals 4 h after an in vivo injection of cycloheximide showed an 80% reduction in glucose transport with no significant change in the cytochalasin B binding density. These results suggest that D-glucose transport in the basolateral membrane is regulated by a combination of a modulation of carriers already in the membrane and subsequent changes in carrier site density.

Intravenous Therapy: Expanding the Bounds of Safety

Intravascular infusion therapy was once a considerable chore. In days gone by, reusable large-bore steel needles made starting infusions a challenge, particularly when they had been transformed into hooks during their previous use. Once in place, needles were secured against all-too-frequent infiltration with elaborate immobilizing constructions of wooden arm boards and yards of adhesive gauze. Infusions were meant to stay in place as long as possible and house officers who developed a talent for placing perpetual infusions were envied by their peers. Over the years, the manufacturers of medical devices provided a continuing series of innovations that made vascular infusion therapy more convenient. Among the first of these was the cheap, disposable needle. Suddenly, all needles were sharp! One of us was a senior medical student when this heaven-sent device first was used at the university hospital. The city hospital downtown, however, was slower to adopt disposable needles. There the

Changes in plasma palmitate specific radioactivity during long-term intravenous infusions of tritiated palmitate into lactating goats

Vascular injection or infusion of isotopically labelled fatty acids into both ruminant and nonruminant species has been used as a method for determining the entry rate of non-esterified fatty acids (NEFA) into blood (Bickerstaffe, Annison & Linzell, 1974; Vranic, 1975). Results obtained in this way represent the release of fatty acids from several sources, principally adipose tissue. The predominant labelled end-products from [3H]– and [14C]fatty acid metabolism are water and carbon dioxide respectively. Both these metabolites enter extensive body pools and the label is unlikely to be reincorporated into plasma NEFA during the time course of conventional short-term experiments (2–4 h). During isotope dilution experiments, however, some labelled fatty acid could be incorporated into adipose tissue triacyglycerol (TAG) following synthesis of low-density lipoprotein in the liver. In addition, the contribution of NEFA carbon to endogenous acetate production could result in transfer of 14C in any C, or 8H attached to the C8 position in acetate, from the infused fatty acid to fatty acids synthesized by liver and adipose tissue.

Protection from irreversible hypoxic injury by potassium cardioplegia and hypothermia: Effects on contracture, morphology and O 2-Enzyme release

Isolated rat hearts were perfused at temperatures from 40 to 30°C in the presence and absence of 16 m m potassium cardioplegia, with hypoxic substrate-free Krebs-Henseleit medium. During hypoxia the development of contracture was monitored with an intraventricular balloon. After intervals from 10 to 300 min of hypoxia hearts were reoxygenated at 37°C and the released creatine kinase activity (CK) was measured for a 15 min interval. At the end of experiments, the percentage of injured cells was estimated by light microscopy. Both hypothermia and cardioplegia delayed the onset and reduced the rate of development of contracture. The effects of cardioplegia and hypothermia were additive. Irreversible injury was delayed proportionally with the delay in full contracture development. Hypothermia caused a progressive decrease in the rate of progression of injury. Cardioplegia also reduced the slopes of injury curves, but its major effect was to delay the onset of injury. Between 40 to 30°C there was a nearly linear decrease in the slopes of injury curves from a rate of 6.6% per min. at 40°C to 0.85% per min. at 30°C. Estimates of injury by CK release and morphology were similar. Severe hypoxic injury was associated with marked reductions in coronary flow rates to about 40% of control flows. In hypoxic hearts at 37°C vascular infusion of colloid carbon demonstrated subendocardial zones of severe ischemia ranging from 10 to 40% of heart ventricular masses. There was no apparent correlation between coronary flow rates and the size of observed perfusion defects. It is concluded that myocardial protection occurs as the combined effect of delaying the onset of injury and slowing its progression after initiation. The proportion of cells in a heart showing morphologic evidence of injury correlated with the observed enzyme release. Injury appeared to progress in quantum steps as individual cells made the transition from reversible to irreversible injury. Reductions in slopes of injury curves with protection could be explained as a slowing of the rate of energy depletion in a heterogenous cell population and a spreading of the time interval over which cells reached a critical level of energy depletion. The existence of perfusion defects and concomitant ischemia may limit the isolated perfused rat heart as an experimental model of hypoxic cell injury.

Topographical appearance of adenohypophysial cells with special reference to the development of the portal system.

To determine whether or not the portal vessels play any essential role on the cytogenesis of adenohypophysis through the mediation of hypothalamic neurohormones, chronological and topographical relations between the portal system and adenohypophysial cells have been studied in fetal rats aged from 14.5 to 18.5, by vascular infusion with India ink and by immunohistochemistry. On day 14.5 the intraglandular fossa (Atwell's recess) receives several blood vessels (primitive portal vessels) from the subtuberal capillary plexus and a pair of fine branches from the internal carotid arteries: those blood vessels anastomose within the recess. On day 15.5 the recess becomes narrow but the vasculature extends posteriorly into the growing anterior wall of the rathke's pouch, in which they sprout short branches showing terminal dilations. Immunoreactive ACTH cells first appear in the ventral-middle portion of the pars distalis, where the vascular sproutings are not evident. On day 16.5 the intraglandular blood vessels spread through the pars distalis and connect occasionally with extraglandular venous system suggesting the initiation of the hypophysial portal circulation. TSH cells first appear sporadically in the posterior part of the pars distalis, where blood vessels are still scarce and very occasional cells abut on te sinusoids. On day 17.5, the recess becomes indistinct and pituitary acquires the mature shape. The intraglandular vasculature of the portal system makes a dense meshwork in the adenohypophysis except the pars intermedia. LH cells appear first in the ventral region of the anterior half of the adenohypophysis, where occasional cells appear abutting on the sinusoids. The conclusion is that the portal blood supply, which might convey hypothalamic neurohormones, is not essential or initial cytogenesis of the adenohypophysial cells studied here.

Serous cysts of the aging guinea pig ovary. III. Permeability of the cyst epithelium to lanthanum and horseradish peroxidase.

The permeability of the epithelium lining serous cysts of the guinea pig ovary was examined using lanthanum and horseradish peroxidase (HRP). Both lanthanum and HRP introduced at the luminal surface of the cyst penetrated to the basal region filling caveolae in both lateral and basal cell surfaces. Within three minutes of vascular infusion of HRP, the tracer was detected between epithelial cells and in caveolae on their lateral and basal surfaces but not associated with intracellular organelles. There was no change in the intracellular distribution of HRP after ten minutes. It was concluded that the epithelium was permeable to the tracers within this time period but that pinocytosis and transport of these tracers through the epithelial cell were not demonstrated.

Modulation of the baroreceptor reflex by angiotensin II and other vasoactive drugs in anaesthetized greyhounds.

1. The effects of vascular infusions of acetylcholine, angiotensin II, noradrenaline and prostaglandin F2 alpha on the baroreceptor reflex were studied in the anaesthetized greyhound. 2. Vertebral artery infusions of low doses of angiotensin II, but not of acetylcholine or prostaglandin F2 alpha, resulted in a significant reduction in the depressor response to carotid sinus nerve stimulation. 3. The increases in blood pressure and heart rate in response to bilateral carotid artery occlusion were not significantly changes during vertebral artery infusions of acetylcholine, angiotensin II or prostaglandin F2 alpha. 4. The increases in blood pressure in response to intravenous infusions of noradrenaline were significantly enhanced during vertebral artery infusions of acetylcholine and angiotensin II, but not of prostaglandin F2 alpha. The bradycardia during noradrenaline infusions was significantly enhanced by angiotensin II alone. 5. The depressor response to carotid sinus nerve stimulation was significantly reduced during intravenous infusions of both noradrenaline and angiotensin II. 6. It is considered that although angiotensin II can be shown to have a specific central action to attenuate the response to carotid sinus nerve stimulation, the role of this action in the complete baroreceptor reflex is unproven.

Ultrastructure of thyroid follicular cells following hypophysial portal vascular infusion of thyrotropin‐releasing hormone

AbstractUltrastructural changes in thyroid follicular cell morphology were studied following the infusion of thyrotropin‐releasing hormone (TRH) for 1 min into a hypophysial stalk portal vessel of adult male rats. At 1, 5, 15 and 30 min following infusion, thyroid glands were removed and prepared for electron microscopic examination. Thyroid follicular cells in unoperated, sham‐operated non‐infused, and saline‐infused control rats were cuboidal, generally lacked intracellular colloid droplets and contained variable numbers of electron‐dense lysosome‐like bodies distributed throughout the cytoplasm. In experimental animals, marked intracellular colloid droplet accumulation was observed 5 min after TRH infusion and remained a constant finding throughout the time‐periods studied. Numerous lysosome‐like dense bodies accumulated in the apical cytoplasm of thyroid follicular cells at 30 min. Fusion of colloid droplets and lysosome‐like bodies had apparently occurred by 30 min. At this time the colloid droplets were smaller, more electron‐dense and were often located more basally within the follicular cell cytoplasm. This study suggests that the morphological response of thyroid follicular cells to hypophysial portal vascular infusion of TRH occurs rapidly and mimics, both temporally and morphologically, the response observed following systemic administration of exogenous TSH.

Effect of the cerebrospinal fluid sink on sucrose-diffusion gradients in brain

The relationship between the measured distribution volume for sucrose in brain and the sink action of CSF was studied in the rabbit by determining the concentration profile of sucrose −14C in the wall of the lateral cerebral ventricle after vascular or ventricular perfusion (or both). Vascular infusion of sucrose resulted in a mean sucrose space of 5.2% with demonstrable diffusion gradients for sucrose in tissue nearest the brain-CSF interface. It was also observed that increasing the bulk loss of sucrose from the ventricular system, by infusing the ventricles with a solution devoid of sucrose, resulted in a fall of the computed brain sucrose space to 2.54%, with the lowest concentration of sucrose in tissue nearest the ependymal and pial surfaces. When the concentration of sucrose in brain equaled that of CSF, after vascular and ventricular infusion of labeled sucrose, the sucrose space measurement increased to 17.2%. These findings support the contention that the magnitude of the brain extracellular space based on the distribution of sucrose between blood and brain does not accurately reflect the anatomical space when the concentration in brain exceeds that of CSF due to the diffusionary losses between the brain and CSF compartments. Conversely, elimination of the sink action of CSF, by equalizing the solute concentration in brain and CSF, results in a computed sucrose space equal to that of the anatomical space.

Effect of temperature and hemoglobin concentration on solubility of O2 in blood.

Effect of temperature and hemoglobin concentration on solubility of O2 in blood.