bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiation of immature enterocytes into enteroendocrine cells byPdx1overexpression
Authors: Yamada Syu , Kojima Hideto , Fujimiya Mineko , Nakamura Takaaki , Kashiwagi Atsunori , Kikkawa Ryuichi
Published: December 2017

The development of a variety of enteroendocrine cells of the gut is poorly understood. We tested whether immature intestinal stem cells were switched to multiple enteroendocrine hormone-producing cells by in vitro transfer of a homeobox gene. We transfected the pancreatic-duodenal homeobox 1 gene ( Pdx1) into IEC-6 cells, an embryonic intestinal epithelial cell line derived from a normal rat, and selected the cells that overexpressed Pdx1 by 150-fold compared with control. The cells were examined for differentiation into enteroendocrine cells by immunocytochemical and electron microscopic analyses. Transfected cells cultured on micropore filters formed a trabecular network piled up on monolayer cells. These trabecular cells showed nuclear localization of Pdx1 protein and contained well-developed rough endoplasmic reticulum as well as many secretory granules of pleomorphic shape in the cytoplasm. Antibodies against chromogranin A, serotonin, cholecystokinin, gastrin, and somatostatin stained these secretory granules in the cytoplasm. Furthermore, immunofluorescence double staining analysis showed that different hormones were produced within a cell. These results provide the evidence that immature intestinal epithelial cells can differentiate into multiple hormone-producing enteroendocrine cells in response to overexpression of Pdx1.
Identification and localization of aquaporin water channels in human salivary glands
Authors: Gresz V. , Kwon T. H. , Hurley P. T. , Varga G. , Zelles T. , Nielsen S. , Case R. M. , Steward M. C.
Published: December 2017

Aquaporin (AQP) water channels are expressed in a variety of fluid-transporting epithelia and are likely to play a significant role in salivary secretion. Our aim was to identify and localize the aquaporins expressed in human salivary glands. Total RNA was extracted from human parotid, submandibular, sublingual, and labial glands and from human brain. Expression of aquaporin mRNA was assessed by RT-PCR using specific primers for human AQP1, AQP3, AQP4, and AQP5. All four aquaporins were detected by RT-PCR in all of the glands, and the sequences were confirmed after further amplification with nested primers. Cleaned PCR products were then used as32P-labeled cDNA probes in a semiquantitative Northern blot analysis using glyceraldehyde-3-phosphate dehydrogenase as reference. Only AQP1, AQP3, and AQP5 mRNAs were present at significant levels. AQP localization was determined by immunohistochemistry on paraffin sections using affinity-purified primary antibodies and peroxidase-linked secondary antibodies. Each salivary gland type showed a broadly similar staining pattern: AQP1 was localized to the capillary endothelium and myoepithelial cells; AQP3 was present in the basolateral membranes of both mucous and serous acinar cells; AQP4 was not detected; and AQP5 was expressed in the luminal and canalicular membranes of both types of acinar cell. We conclude that AQP3 and AQP5 together may provide a pathway for transcellular osmotic water flow in the formation of the primary saliva.
Fatty liver vulnerability to endotoxin-induced damage despite NF-κB induction and inhibited caspase 3 activation
Authors: Yang Shiqi , Lin Huizhi , Diehl Anna Mae
Published: December 2017

Fatty livers are sensitive to lipopolysaccharide (LPS) damage. This study tests the hypothesis that this vulnerability occurs because protective, antiapoptotic mechanisms are not upregulated appropriately. Genetically obese, leptin-deficient ob/ob mice, a model for nonalcoholic fatty liver disease, and their lean litter mates were treated with a small dose of LPS. General measures of liver injury, early (i.e., cytochrome c release) and late (i.e., activation of caspase 3) events that occur during hepatocyte apoptosis, and various aspects of the signal transduction pathways that induce nuclear factor-κB (NF-κB) and several of its antiapoptotic transcriptional targets (e.g., inducible nitric oxide synthase, bfl-1, and bcl-xL) were compared. Within 0.5–6 h after LPS exposure, cytochrome c begins to accumulate in the cytosol of normal livers, and procaspase 3 cleavage increases. Coincident with these events, kinases (e.g., AKT and Erk-1 and -2) that result in the degradation of inhibitor κ-B are activated; NF-κB activity is induced, and NF-κB-regulated gene products accumulate. Throughout this period, there is negligible histological evidence of liver damage, and serum alanine aminotransferase values barely increase over baseline values. Although ob/ob livers have significant histological liver injury and 11-fold greater serum alanine aminotransferase values than those of lean mice by 6 h post-LPS, they exhibit greater activation of AKT and Erk, more profound reductions in inhibitor κ-B, enhanced activation of NF-κB, and greater induction of NF-κB-regulated genes. Consistent with this heightened antiapoptotic response, increases in cytochrome c and procaspase 3 cleavage products are inhibited. Together with evidence that ob/ob hepatocytes have a reduced ATP content and undergo increased lysis after in vitro exposure to tumor necrosis factor-α, these findings suggest that fatty livers are sensitive to LPS damage because of vulnerability to necrosis, rather than because of apoptosis.
Abnormalities of gallbladder muscle associated with acute inflammation in guinea pigs
Authors: Xiao Zuo-Liang , Chen Qian , Biancani Piero , Behar Jose
Published: December 2017

Muscle strips from experimental acute cholecystitis (AC) exhibit a defective contraction. The mechanisms responsible for this impaired contraction are not known. The present studies investigated the nature of these abnormalities. AC was induced by ligating the common bile duct of guinea pigs for 3 days. Contraction was studied in enzymatic dissociated muscle cells. Cholecystokinin (CCK) and prostaglandin E2(PGE2) receptor binding studies were performed by radioreceptor assay. The levels of lipid peroxidation, cholesterol, phospholipid, and H2O2as well as the catalase and superoxide dismutase (SOD) activities were determined. PGE2content was measured by radioimmunoassay. Muscle contraction induced by CCK, ACh, or KCl was significantly reduced in AC, but PGE2-induced contraction remained normal. GTPγS, diacyglycerol (DAG), and 1,4,5-trisphosphate (IP3), which bypass the plasma membrane, caused a normal contraction in AC. The number of functional receptors for CCK was significantly decreased, whereas those for PGE2remained unchanged in AC. There was a reduction in the phospholipid content and increase in the level of lipid peroxidation as well as H2O2content in the plasma membrane in AC. The PGE2content and the activities of catalase and SOD were also elevated. These data suggest that AC cause damage to the constituents of the plasma membrane of muscle cells. The preservation of the PGE2receptors may be the result of muscle cytoprotection.
Activation of poly(ADP-ribose) polymerase in severe hemorrhagic shock and resuscitation
Authors: Watts John A. , Grattan Robert M. , Whitlow Bradley S. , Kline Jeffrey A.
Published: December 2017

This study examines activation of poly(ADP-ribose) polymerase (PARP) in the ileum during hemorrhage and resuscitation and determines if inhibition of PARP reduces organ dysfunction and metabolic acidosis. Awake, nonheparinized rats were hemorrhaged (40 mmHg, 60 min). Resuscitation used Ringer's solution (2[Formula: see text] × shed volume) and packed red blood cells ([Formula: see text]shed volume). Ileal PARP activity was elevated at the end of hemorrhage (3.6-fold) and 10 min of resuscitation (5-fold). The subsequent decline in PARP activity observed after 60 min of resuscitation was not due to cleavage by caspase-3. Ileum permeability increased 10-fold and circulating liver enzymes increased 4- to 6-fold following 60 min of resuscitation in animals pretreated with 3-aminobenzoic acid, a structural analog that does not inhibit PARP. Pretreatment with 3-aminobenzamide (3-AB), a PARP inhibitor, reduced these changes, whereas posttreatment with a bolus of 3-AB was ineffective. Metabolic acidosis, accumulation of lactate, and base deficit was reduced by pretreatment with 3-AB. PARP is activated in the ileum by hemorrhage and by resuscitation. Activation of PARP contributes to organ dysfunction in the ileum and liver and appears to be central to the development of metabolic acidosis.
HCl causes less intracellular acidification inNecturusgastric mucosa surface epithelial cells than other acids
Authors: Nylander-Koski O. , Mustonen H. , Vikholm I. , Kiviluoto T. , Kivilaakso E.
Published: December 2017

Luminal acid causes intracellular acidification in the gastric epithelium, but the mechanism by which H+enters surface cells remains obscure. This study addressed the problem by assessing how different acids affect intracellular pH in gastric surface cells. Isolated Necturus maculosus antral mucosa was exposed to HCl, HNO3, H2SO4, and H3PO4at pH 2.30. Intracellular pH was measured with microelectrodes. The physicochemical interaction of a synthetic model of gastric phospholipids with the different acids was studied using Langmuir film balance. Exposure to luminal HNO3, H2SO4, or H3PO4caused significantly larger intracellular acidification than exposure to HCl. The degree of acidification was not dependent on the valence or nature of the anionic counterion of the acid but significantly correlated with the amount of molecular acid. By Langmuir film balance, subphases acidified with HNO3, H2SO4, or H3PO4caused more close packing of phospholipid molecules than those acidified with HCl, possibly allowing hydrogen bonding between head groups to facilitate H+movement across the phospholipid membrane. HCl causes significantly less intracellular acidification in gastric epithelium than HNO3, H2SO4, or H3PO4. This may be caused by the lower amount of molecular HCl in solution and possible hydrogen bonding between the head groups of phospholipid molecules and the other acids.
Cold preservation-warm reoxygenation increases hepatocyte steady-state Ca2+ and response to Ca2+-mobilizing agonist
Authors: Elimadi Aziz , Haddad Pierre S.
Published: December 2017

Although the role of Ca2+ in liver transplantation injury has been the object of several studies, direct evidence for alterations in intracellular Ca2+ homeostasis after cold preservation-warm reoxygenation (CP/WR) has never been presented. We thus investigated the effects of CP/WR on steady-state Ca2+ and responses to a Ca2+-mobilizing agonist. Isolated rat hepatocytes were suspended in University of Wisconsin solution, stored at 4°C for 0, 24, and 48 h, and reoxygenated at 37°C for 1 h. Cytosolic Ca2+ was measured in single cells by digitized fluorescence videomicroscopy. CP/WR caused a significant increase in steady-state cytosolic Ca2+, which was inversely proportional to cell viability. Pretreatment of hepatocytes with an agent that protects mitochondrial function attenuated the increase in steady-state cytosolic Ca2+ and improved hepatocyte viability. Ca2+responses to the purinergic agonist ATP also increased significantly as a function of cold storage time. This increase was related to an increase in the size of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores and subsequent capacitative Ca2+entry. Thus CP/WR significantly perturbs steady-state hepatocellular Ca2+ and responses to Ca2+-mobilizing agonists, which may contribute to hepatocyte metabolic dysfunction observed after CP/WR.
PACAP stimulates gastric acid secretion in the rat by inducing histamine release
Authors: Sandvik Arne K. , Cui Guanglin , Bakke Ingunn , Munkvold Bjørn , Waldum Helge L.
Published: December 2017

Previous studies have shown that pituitary adenylate cyclase-activating peptide (PACAP) stimulates enterochromaffin-like (ECL) cell histamine release, but its role in the regulation of gastric acid secretion is disputed. This work examines the effect of PACAP-38 on aminopyrine uptake in enriched rat parietal cells and on histamine release and acid secretion in the isolated vascularly perfused rat stomach and the role of PACAP in vagally (2-deoxyglucose) stimulated acid secretion in the awake rat. PACAP has no direct effect on the isolated parietal cell as assessed by aminopyrine uptake. PACAP induces a concentration-dependent histamine release and acid secretion in the isolated stomach, and its effect on histamine release is additive to gastrin. The histamine H2antagonist ranitidine potently inhibits PACAP-stimulated acid secretion without affecting histamine release. Vagally stimulated acid secretion is partially inhibited by a PACAP antagonist. The results from the present study strongly suggest that PACAP plays an important role in the neurohumoral regulation of gastric acid secretion. Its effect seems to be mediated by the release of ECL cell histamine.
Mucosal acid challenge activates nitrergic neurons in myenteric plexus of rat stomach
Authors: Schicho Rudolf , Schemann Michael , Holzer Peter , Lippe Irmgard T.
Published: December 2017

We tested the hypothesis that intrinsic neurons of the rat gastric myenteric plexus can be activated by an acid (HCl) challenge of the mucosa. Activated neurons were visualized by immunohistochemical detection of c-Fos, a marker for neuronal excitation. The neurochemical identity of the neurons activated by the HCl challenge was determined by colocalizing c-Fos with a marker for excitatory pathways, choline acetyltransferase (ChAT), and a marker for inhibitory pathways, nitric oxide synthase (NOS). Two hours after intragastric administration of HCl or saline, stomachs were removed and immunofluorescence triple labeling of myenteric neurons was carried out on whole mount preparations. Treatment with 0.35, 0.5, and 0.7 M HCl induced c-Fos in 8%, 56%, and 64%, respectively, of NOS-positive but not ChAT-positive neurons. c-Fos was also seen in glial cells of HCl-treated rats, whereas in saline-treated animals c-Fos was absent from the myenteric plexus. HCl treatment did not change the proportion of ChAT- and NOS-immunoreactive neurons in the myenteric ganglia. It is concluded that gastric acid challenge concentration-dependently stimulates a subpopulation of nitrergic, but not cholinergic, myenteric plexus neurons, which may play a role in muscle relaxation, vasodilatation, and/or secretion.
III. Interaction of interstitial cells of Cajal with neuromediators: an interim assessment
Authors: Daniel E. E.
Published: December 2017

Interstitial cells of Cajal (ICC) control gastrointestinal motility; some pace slow waves and others act in enteric neurotransmission. This review asks the question, does either class of ICC receive and respond to messages carried by neuromediators from these nerves? Relevant evidence includes the presence of receptors or responses to exogenous neuromediators and responses to endogenous neuromediators. Some pacemaking ICC networks have receptors for or respond to some exogenous neuromediators. None is known to respond to endogenous neuromediators. Intramuscular ICC have receptors for and respond to some neuromediators and are required in mice for responses to the exogenous and endogenous neuromediators nitric oxide and acetylcholine. The mechanisms underlying this requirement remain unclear. ICC pathologies exist, but their origins are unknown.
Effects of glutamine deprivation on protein synthesis in a model of human enterocytes in culture
Authors: Le Bacquer Olivier , Nazih Hassan , Blottière Hervé , Meynial-Denis Dominique , Laboisse Christian , Darmaun Dominique
Published: December 2017

To assess the effect of glutamine availability on rates of protein synthesis in human enterocytes, Caco-2 cells were grown until differentiation and then submitted to glutamine deprivation produced by exposure to glutamine-free medium or methionine sulfoximine [l- S-[3-amino-3-carboxypropyl]- S-methylsulfoximine (MSO)], a glutamine synthetase inhibitor. Cells were then incubated with2H3-labeled leucine with or without glutamine, and the fractional synthesis rate (FSR) of total cell protein was determined from2H3-labeled enrichments in protein-bound and intracellular free leucine measured by gas chromatography-mass spectrometry. Both protein FSR (28 ± 1.5%/day) and intracellular glutamine concentration (6.1 ± 0.6 μmol/g protein) remained unaltered when cells were grown in glutamine-free medium. In contrast, MSO treatment resulted in a dramatic reduction in protein synthesis (4.6 ± 0.6 vs. 20.2 ± 0.8%/day, P < 0.01). Supplementation with 0.5–2 mM glutamine for 4 h after MSO incubation, but not with glycine nor glutamate, restored protein FSR to control values (24 ± 1%/day). These results demonstrate that in Caco-2 cells, 1) de novo glutamine synthesis is highly active, since it can maintain intracellular glutamine pool during glutamine deprivation, 2) inhibition of glutamine synthesis is associated with reduced protein synthesis, and 3) when glutamine synthesis is depressed, exogenous glutamine restores normal intestinal FSR. Due to the limitations intrinsic to the use of a cell line as an experimental model, the physiological relevance of these findings for the human intestine in vivo remains to be determined.
Electrophysiological and anatomical observations on the heart of the African lungfish
Authors: Arbel E. R. , Liberthson R. , Langendorf R. , Pick A. , Lev M. , Fishman A. P.
Published: December 2017

Electrophysiological and histological observations were made on the heart of the African lungfish. Impulse origin and propagation were studied using simultaneously recorded epicardial and pericardial electrograms. The primary pacemaker site in the lungfish was found to be at the sinus venosus at its junction with the left cardinal vein. Under a variety of circumstances, pacemaker function shifted to other sites. In response to stress, probably under vagal influence, the regular and rapid sinus venosus rate was generally superseded by an irregular and slower atrial pacemaker. Heart rate and sinoatrial and atrioventricular conduction times varied with changes in temperature [Q10=3.77, 2.55, and 5.46, respectively]. Although alterations in impulse formation and conduction did occur, the site of impulse formation and the patterns of conduction between heart chambers were usually fixed, implying the existence of an organized conduction system. Nonetheless, extensive histological study failed to disclose either organized nodal structures or specialized conduction pathways.
Effect of autonomic blockade on the hemodynamic findings in acute cardiac tamponade
Authors: Friedman H. S. , Lajam F. , Zaman Q. , Gomes J. A. , Calderon J. , Marino N. D. , Fernando H. A. , Choe S. S.
Published: December 2017

Twenty-three closed-chest, alpha-chloralose-anesthetized, volume-expanded, alpha- and beta-adrenergic-blockaded dogs with rate fixed by atrial pacing had 30-90 ml of saline at 37 degrees C infused into the pericardial sac a) with vagus intact, b) after vagotomy, and c) with vagus intact but with systolic pressure augmented with a balloon. A significant reduction in left ventricular (LV) systolic pressure (SP), and cardiac output (CO) occurred at a pericardial volume of 30-60 ml, when LV end-diastolic (ED) and right atrial (RA) pressures were not increased. Whereas the percentage decline of CO, LVSP, maximum negative and maximum positive dP/dt was greater in group A (vagus intact) than in group B (vagus cut), significant residual depressed performance was demonstrated only in group B. In four paced, atropinized, beta-blockaded dogs, response to tamponade was similar to that in intact dogs; vagotomy at 90 ml in these dogs resulted in a fall in CO, a rise of LVSP and a significant elevation in LVED and RA pressures. Thus, in the early phases of cardiac tamponade a sympathetic neurohumoral response supports cardiac performance while the vagus nerve exerts a myocardial protective effect. Vagal afferents appear to modulate this response.
Measurement of intrarenal anatomic distribution of krypton-85 in endotoxic shock in dogs
Authors: Passmore J. C. , Neiberger R. E. , Eden S. W.
Published: December 2017

Renal blood flow distribution was measured in control dogs and dogs in endotoxic shock by utilizing a modification of 85Kr washout. Kidneys, injected with 85Kr via a renal arterial cannula, were removed at several specific intervals after injection, rapidly frozen, and sectioned transversely so that pieces of tissue could be isolated and counted for radioactivity. Control outer cortical blood flow was 462 ml/min per 100 g tissue wt, but 122 ml/min per 100 g during shock. Control inner cortical outer medullary flow was 396 ml/min per 100 g, but 166 ml/min per 100 g in shock. Control flow in the inner stripe of the outer zone of the medulla was 130 ml/min per 100 g and 134 ml/min per 100 g in shock. In shock the initial volume of radioactivity distributed to outer cortex was smaller, to inner cortex the same, and to inner stripe outer zone of the medulla larger than in controls. This study delineates renal washout of 85Kr from specific areas of the kidney and indicates the alterations in extent and magnitude of this washout in endotoxic shock.
Identification of smooth muscle series elastic component in intact carotid artery
Authors: Dobrin P. , Canfield T.
Published: December 2017

Experiments were performed to indentify the series elastic component (SEC) in intact dog carotid artery held at in situ length. The vessels were studied during excitation of the muscle with norepinephrine and after metabolic poisoning with potassium cyanide and sodium iodoacetate. Static circumferential stress-strain curves and stress-quick-release stiffness curves were examined to evaluate Maxwell and Voigt model elements. The vessels were studied at 33, 36, and 39 degrees C. Temperature variations altered active stress, but did not alter connective tissue properties or the Maxwell SEC stiffness. The Voigt model SEC stiffness was altered, but this was secondary to changes in active stress. Thus, most of the SEC is separate from the contractile apparatus. Other vessels were treated with elastase, collagenase, or hyaluronidase to digest the connective tissue components of the wall. Hyaluronidase had no effect on mechanics. Elastase and collagenase altered connective tissue properties, but only elastase unequivocally altered SEC stiffness. This analysis indicated 1) that the carotid artery wall is better represented by a Maxwell model than a Voigt model, and 2) that the SEC in intact carotid artery is primarily elastin.
Simultaneous regional myocardial blood flows by tritiated water and microspheres
Authors: Tripp M. R. , Meyer W. , Einzig S. , Leonard J. J. , Swayze C. R. , Fox I. J.
Published: December 2017

Regional myocardial blood flow (RMF) was measured simultaneously by use of labeled 8-mum microspheres and the constant-rate infusion of 3H2O in 22 open-chest dogs (Na pentobarbital anesthesia) under markedly different hemodynamic conditions. Following cardiac excision, three adjacent 80-mg tissue samples were taken from the subendocardial, mid-wall, and subepicardial layers of quadrantal left ventricular (LV) segments of the basal and midventricular cardiac slices, and from one segment of the apical slice, totaling 81 samples per LV. RMF was calculated by the microsphere reference-flow technique and by two 3H2O tissue-uptake models. Good agreement between techniques (r=0.9-0.96) was found in comparing flows to the myocardial layers. Using Kety's "single-mixer" model of 3H2O tissue uptake, fairly good agreement was found between techniques in the 80-mg tissue samples; the cofficient of variation from regression was 18.5% which improved markedly to 12.3% when the flow values for each technique were averaged in the three adjacent samples. Analysis of variance showed that flow to the various LV subdivisions (layer, segment, slice) of control animals was heterogeneous.
Hypercapnia and right-duct lymph flow in pups and adult dogs
Authors: Stinson D. A. , Taylor P. M. , Rees E. P. , Boonyaprakob U.
Published: December 2017

The effect of moderate hypercapnia on right-thoracic duct lymph flow, pulmonary hemodynamics, and lung water content was studied in seven 2- to 5-wk-old dogs and eleven adult dogs anesthetized with pentobarbital, paralyzed with succinylcholine, and maintained on intermittent positive-pressure ventilation. Following a 30-min control period in which arterial pH and blood gases were maintained within normal limits, the dogs were ventilated with 3-14% CO2 for 30 min; they were then returned to control conditions fro a 30-min recovery period. Hypercapnia was associated with a significant increase in lymph flow rate in both pups and adult dogs (P less than 0.05) and a significant increase in pulmonary artery and pulmonary artery wedge pressures in adult dogs (P less than 0.05). These data suggest that hypercapnia may increase the net flow of water out of the pulmonary vascular bed.
Vasopressin and angiotensin: reciprocal mechanisms controlling mesenteric conductance
Authors: McNeill J. R. , Wilcox W. C. , Pang C. C.
Published: December 2017

Intravenous infusions of [Sar1-Ala8]angiotensin II, acute hypophysectomy, and acute intestinal denervation were carried out in 15 pentobarbital-anesthetized cats. Infusion of the angiotensin II antagonist caused only a small increase in superior mesenteric arterial conductance and a small decrease in arterial pressure in intact animals, but the changes were subypophysectomy alone caused only a small intestinal vasodilatation and little change in arterial pressure. However, the responses to hypophysectomy were much larger when the gland was removed during a prolonged infusion of the angiotensin II antagonist. Intestinal denervation caused only minor changes in mesenteric conductance and arterial pressure, and the responses to [Sar1-Ala8]angiotensin II and hypophysectomy were largely unaltered by the presence or absence of the intestinal innervation. The results suggest that the renin-angiotensin and vasopressin systems are reciprocal overlapping mechanisms that exert a significant vasoconstrictor influence on the intestinal resistance vessels in the anesthetized cat. In the absence of one control system, the other appears to compensate to maintain resistance.
Inhibition of endo- and epicardial glycogenolysis by propranolol in ischemic hearts
Authors: Ichihara K. , Abiko Y.
Published: December 2017

The effect of coronary artery ligation on myocardial glyocogenolysis was studied in the endo- and epicardial layers of the left ventricle in dogs pretreated with saline or 1 mg/kg of propranolol. Coronary artery ligation was performed by ligating one of the small branches of the left anterior descending coronary artery. Even after coronary artery ligation, neither increase in phosphorylase activity nor breakdown of glycogen was observed in both layers of ischemic region of myocardium in propranolol-pretreated dogs. These results indicate that pretreatment with propranolol inhibits the increase in glycogenolysis being caused by coronary artery ligation. Propranolol howefer, did not inhibit completely the coronary artery ligation-induced increase in glucose 6-phosphate and lactate and decrease in phosphocreatine in the myocardium, especially in the endocardial layers.
Cerebral blood flow during hemorrhagic hypotension in the unanesthetized goat
Authors: Gomez B. , Vallejo A. R. , Alborch E. , Dieguez G. , Lluch S.
Published: December 2017

Changes in cerebral blood flow (CBF), arterial blood pressure (AP), and cardiac output (CO) were studied during stepwise blood losses in 12 unanesthetized goats. Bleeding was followed by a drop in CBF, AP and CO in a nearly parallel fashion. Control values (means +/- SE) for CBF, AP, and CO were 117 +/- 5.6 ml/min per 100 g, 105 +/- 3.1 mmHg, and 2,825 +/- 124 ml/min, respectively; and after bleeding, 66 +/- 3.9 ml/min per 100 g, 57 mmHg, and 1, 383 ml/min. Arterial blood samples obtained before bleeding, during the hypotensive state, and after reinfusion did not show any significant differences in pH, PCO2, and PO2 values. In phentolamine-treated animals, bleeding produced a drop in AP and CO similar to that observed in the nontreated animals; however, the decrease in CBF was less marked. These findings show that CBF follows pari passu the fall in AP, and they indicate that the alpha-adrenergic receptors of the cerebral vessels are involved in the cerebral blood flow changes in hemorrhage.
Computer simulation of ischemic rat heart purine metabolism. I. Model construction
Authors: Kohn M. C. , Garfinkel D.
Published: December 2017

A model is proposed for the partial depletion of the adenine nucleotide pool in the ischemic perfused rat heart which involves seven enzymes: adenylate cyclase, 3',5'-cyclic AMP phosphodiesterase, 5'-nucleotidase, adenosine kinase, adenosine deaminase, purine nucleoside phosphorylase, and inorganic pyrophosphatase. The computer implementation of this model is in terms of rate laws, several of which were obtained by a systematic least-squares fitting procedure. Depletion of the adenine nucleotide pool is initiated by the release of endogenous noradrenaline into the interstitial fluid, which results from a fall in tissue PO2, and the subsequent activation of adenylate cyclase. In this model the substrate for 5'-nucleotidase is a membrane-bound AMP pool formed by hydrolysis of extracellular fluid and functions as a vasodilator; excess adenosine is incorporated into the tissue by a "permease" with Michaelis-Menten kinetics and converted to AMP, inosine, and hypoxanthine. Alternative mechanisms, such as the deamination of AMP by adenylate deaminase and conversion of AMP to adenine by AMP pyrophosphorylase, were rejected primarily on qualitative biochemical grounds.
A solid-state arteriovenous oxygen difference analyzer for flowing whole blood
Authors: Shepherd A. P. , Burgar C. G.
Published: December 2017

This communication describes a spectrophotometric device which determines the arteriovenous oxygen difference (a-v O2) on whole blood flowing through optical cuvettes. The instrument consists entirely of commercially available solid-state components, including the light sources, light-emitting diodes. When calibrated against conventional determinations of blood oxygen content, the output of the a-v O2 analyzer was shown to be highly linear and to be independent of total hemoglobin concentration. The electronic circuit, the theory of the measurement, and sources of error are described in detail.
Elevation of arterial blood pressure in the squirrel monkey at 10 degrees C
Authors: Wasserstrum N. , Herd J. A.
Published: December 2017

Systemic arterial blood pressure, heart rate, and total body oxygen consumption were measured in seven unanesthetized squirrel monkeys exposed to ambient temperatures of 28 degrees C and 10 degrees C. At 28 degrees C, subjects sat quietly, the average mean arterial blood pressure was 116 +/- 16 (mean +/- SD, n - 7) mmHg, heart rate was 274 +/- 31 beats/min, and oxygen consumption was 14 +/- 1.4 ml/kg-min. At 10 degrees C, the animals shivered vigorously, the average mean arterial blood pressure was 139 +/- 16 mmHg, heart rate was 328 +/- 18 beats/min, and oxygen consumption was 31.6 +/- 3.9 ml/kg-min. Thus, the oxygen consumption more than doubled, the blood pressure rose by approximately 21%, and the heart rate by approximately 20%. Elevations in heart rate as well as systemic mean arterial blood pressure during exposure to low ambient temperature were probably mediated by sympathetic-adrenal discharges as well as by activity of skeletal muscles.
Fibrinogen synthesis in rabbits: effects of altered levels of circulating fibrinogen
Authors: Alving B. M. , Bell W. R. , Evatt B. L.
Published: December 2017

The effects of altered fibrinogen concentrations on fibrinogen synthesis in rabbits were evaluated by determining the rate of appearance of [75Se]selenomethionine (75SeM) in circulating fibrinogen. Fibrinogen levels were maintained at twice normal by infusion of homologous fibrinogen for either 1 or 6 days before the intravenous injection of 20 micronCi of 75SeM, and the rate of appearance of labeled fibrinogen was measured during the subsequent 24 h. In both groups, synthesis was unchanged. Five hours after induction of partial defibrinogenation by the infusion of bovine thrombin, fibrinogen synthesis was increased threefold. Stimulation was not attributable to decreased fibrinogen concentrations; synthesis was increased equally when levels were maintained above normal by infusion of fibrinogen before administration of thrombin. Heat-inactivated thrombin and diisopropylfluorophosphate-inactivated thrombin did not stimulate fibrinogen synthesis. Thrombin produced elevated titers of fibrinogen-fibrin degradation products (FDP-fdp). However, fibrinogen synthesis was not increased in rabbits that had received FDP-fdp from thrombin-treated donors. These data suggest that neither the fibrinogen concentration nor FDP-fdp influenced fibrinogen synthesis.
42K exchange during myocardial ischemia
Authors: Shine K. I. , Douglas A. M. , Ricchiuti N.
Published: December 2017

42K exchange was studied before and after total ischemia in isolated, blood-perfused rabbit interventricular septa at 37 degrees C and 72 beats/min. Of 11 septa made ischemic for up to 45 min after 42K labeling to asymptotic values, 10 showed no decline in 42K as measured by tissue probe counts 5 min after reperfusion. Of these 10 septa, 7 showed a 1.4-14.2% increase in 42K counts on reperfusion. Three of four muscles reperfused after 60 min of ischemia showed progressive 42K losses. Of 14 septa previously labeled with 42K, 9 showed a parallel decrease in 42K-exchange rate constants as measured by tissue probe and effluent during washing out after 2-45 min of ischemia. In five other muscles a nonparallel decrease in rate constants as measured by tissue probe and effluent during washout indicated inhomogeneity of 45K exchange. These results indicated no persistent impairment in Na pump activity for 30-45 min of total ischemia. After ischemia for 45 min or less there was no consistent relationship between recovery of mechanical function and preservation of 42K content. After 60 min of ischemia, irreversible mechanical injury was associated with loss of tissue potassium.
Role of fibrinopeptide B release: comparison of fibrins produced by thrombin and Ancrod
Authors: Shen L. L. , Hermans J. , McDonagh J. , McDonagh R. P.
Published: December 2017

The gelation time, opacity, light scattering, and elastic moduli of human fibrin gels clotted in the presence of thrombin, Ancrod, and Reptilase have been compared. At low ionic strength lateral association to thick fibers is observed in all cases. At all ionic strengths thrombin fibrin forms thicker fibers than does Ancrod fibrin. We have demonstrated that an increase in the extent of lateral association is linked to an increase in its velocity and to a decrease in the gelation time. One may consider the removal of fibrinopeptide B to act as a switch: after it is removed fibrin assembles rapidly to thick fibers and gelation is fast; but when this peptide is still attached, there is a slow assembly of thin fibers, and gelation, especially of dilute fibrin, is delayed. We believe that this delay is critical for the complete digestion by plasmin of fibrin formed during in vivo defibrination with Ancrod and of fibrin produced by very small amounts of thrombin (which would still contain fibrinopeptide B), and that slow release of fibrinopeptide B is part of a control mechanism for the regulation of fibrin formation and the prevention of intravascular coagulation.
Cardiopulmonary baroreflexes: left ventricular effects
Authors: Lloyd T. C.
Published: December 2017

Systemic vascular resistance of dogs perfused at constant arterial pressure by a pump oxygenator was used as a measure of left ventricular baroreflexes initiated by imposing pressure changes on the beating, as well as on the fibrillating, ventricle. In the unloaded beating heart mean left atrial and systolic ventricular pressures averaged 0.3 and 24 mmHg, respectively. Afterloads and preloads that increased systolic pressure to 63 mmHg while raising mean atrial pressures to 3.3 and 1.7 mmHg, respectively, had no effect on resistance. However, pressurization of the fibrillating ventricle caused vasodepressor responses proportional to the stimulus. The ventricular baroreflex had a significantly lower sensitivity and higher threshold than the vasodepressor reflex observed when simultaneously pressurizing the fibrillating ventricle, beating atrium, and lung vessels. On the basis of wall tension, the results are consistent with other reports that have shown ventricular baroreflexes to be initiated by systolic pressure in the range 100-150 mmHg, but not by diastolic pressure in the range 10-20 mmHg. A more sensitive reflex, able to respond to changes of ventricular filling pressure, arises from the left atrium and pulmonary veins.
Transmural myocardial perfusion during restricted coronary inflow in the awake dog
Authors: Bache R. J. , McHale P. A. , Greenfield J. C.
Published: December 2017

Phasic coronary flow and transmural myocardial perfusion were studied during coronary artery constriction in 10 dogs with electromagnetic flowmeters and hydraulic occluders on the left circumflex coronary artery. Regional blood flow was estimated using left atrial injections of radionuclide-labeled microspheres 9 micron in diameter. During control conditions, 14+/-0.7% of coronary flow occurred in systole and subendocardial (endo) flow exceeded subepicardial (epi) flow in the region of the posterior papillary muscle (endo/epi=1.16). Immediately following partial inflation of the occluder to reduce coronary inflow 39+/-3%, systolic flow was unchanged while diastolic flow fell 42+/-3%, thereby increasing the portion of flow in systole to 22+/-1.4%. At this time blood flow was reduced nearly uniformly across the wall of the left ventricle. When coronary constriction was maintained for 30 s, an additional shift of flow from diastole to systole occurred (systolic flow=29+/-2.3% of total inflow), and transmural perfusion was redistributed from subendocardium to subepicardium (endo/epi=0.37). This redistribution of flow was accompanied by a fall in coronary pressure distal to the occluder, indicating vasodilation of the distal coronary vasculature.
Effect of stimulation of hepatic nerves on hepatic O2 uptake and blood flow
Authors: Lautt W. W.
Published: December 2017

Acute denervation of the liver did not result in changes of oxygen uptake or hemodynamics in the intact liver of the cat. Stimulation of the hepatic nerves resulted in a marked reduction of vascular conductance of the hepatic artery and portal vein (intrahepatic) resulting in almost complete cessation of arterial flow and increased portal blood pressure. The hepatic artery showed a more complete escape from the neurogenic vasoconstriction than did the portal vein. During the stable "escape phase" oxygen delivery was 86% of control, but hepatic extraction of oxygen increased so that oxygen uptake was not altered from control values. The return of oxygen consumption to normal during nerve stimulation suggests that redistribution of hepatic blood flow did not occur. In spite of arterial and portal venous blood pressure changes and changes in gut conductance, oxygen extraction of the gut did not change.
Heart rate and oxygen uptake response to angiotensin in the squirrel monkey at 10 degrees C
Authors: Wasserstrum N. , Herd J. A.
Published: December 2017

Unanesthetized squirrel monkeys exposed to an ambient temperature of 10 degrees C showed elevations in total body oxygen consumption (VO2), systemic arterial blood pressure (BP), and heart rate (hr) above values recorded at 28 degrees C. Further elevation of BP in the cold by intravenous infusion of phenylephrine (5-50 microgram/kg-min) was accompanied by reduction in both VO2 and HR, and the changes in VO2 were proportional to those in HR. When BP was raised by intravenous infusion of angiotensin (0.05-1.0 microgram/kg-min), large elevations in BP were again accompanied by reductions in HR and VO2. However, for equivalent elevations in BP, the depressions in both HR and VO2 were much smaller with angiotensin than they were with phenylephrine. Previous studies in this laboratory have demonstrated that in response to experimental elevation of BP, reflexes originating at the sinoaortic baroreceptors depress not only HR but also VO2. The present results suggest that angiotensin modulates baro-reflexive responses to elevation in BP. The reductions in HR and VO2 that ordinarily occur in response to baroreceptor stimulation may be modified by an action of angiotensin on the central nervous system.
Relation of proteins, platelets, and gas nuclei in adhesion to a synthetic material
Authors: Ward C. A. , Stanga R. D. , Zingg W. , Herbert M. A.
Published: December 2017

We report the result of exposing silicone rubber to washed pig platelet suspensions that contained on average 0.018 mg of proteins/ml in solutions. This protein content is sufficiently low to reasonably neglect the protein adhesion to the material. On comparing the measured platelet adhesion from the platelet suspensions with that from blood, we find that when the gas nuclei normally present in the surface roughness of the material are removed the number of adhering platelets is the same. Thus, in the absence of the gas nuclei, the proteins in blood plasma play a negligible role in the platelet adhesion. In contrast, when both the gas nuclei and proteins are present, the maximum platelet adhesion was observed. From this and the above observation, it appears the gas nuclei affect one or more of the proteins, and this brings about an increased platelet adhesion. Finally, the platelet adhesion from the platelet suspensions was reduced after the removal of the gas nuclei. Thus the platelets themselves sense the change in the surface resulting from the removal of the gas nuclei.
Determinants of isogravimetric capillary pressure in the isolated dog hindlimb
Authors: Brace R. A. , Guyton A. C. , Taylor A. E.
Published: December 2017

The hindlimb of the dog was rapidly isolated and carefully perfused in an attempt to prevent transcapillary fluid shifts into the interstitium which may occur during normal surgical isolation and perfusion. In the control preparation before weight was allowed to increase, isogravimetric capillary pressure (Pci) averaged 8 mmHg lower than colloid osmotic pressure of the plasma (IIp). As the weight of the leg was increased, Pci increased and IIp - Pci decreased. When weight was increased by 5.8%, IIp - Pci averaged 3 mmHg; with a 9.8% increase in weight, IIp - Pci averaged 1.3 mmHg. The calculated value of compliance of the interstitial space averaged 0.50 ml/mmHg per 100 g of tissue and increased approximately 10-fold as the weight of the leg was increased. Since IIp - Pci has always been reported to be approximately 2 mmHg when the hindleg was isolated with standard surgical techniques, these data suggest that the procedures normally used to isolate and perfuse the hindlimb caused the weight of the limb to increase by 6% or more before Pci was determined. Furthermore, it appears that most of the variation in the reported value of Pci is due to variation in the value of IIp since IIp - Pci has always been reported to be very close to 2 mmHg in the isolated hindlimb.
Nonexcised papillary muscle preparation: force and length measurement and control
Authors: Suga H. , Nakayama K. , Sagawa K.
Published: December 2017

An electromechanical servocontrol system was developed to analyze mechanical properties of a nonexcised, blood-perfused papillary muscle. A miniature load cell mounted on the moving arm of a pen motor measured muscle force, and a shaft angle sensor built in the motor measured the length. The pen motor was actuated by a servocontrol command signal. A papillary muscle was exposed in the right ventricle of an excised, cross-circulated canine heart. The tendinous end of the papillary muscle was connected to the load cell. The intact root of the muscle was fixed by a metal ring. The preparation was stable over 5 h heating at a regular spontaneous heart rate (95-150/min) at 37 degrees C. The system allowed the muscle to contract in various modes such as isometric, isotonic, auxotonic, afterloaded isotonic, quick released, lengthening, etc. Changes in the contraction mode, preload, and afterload could be achieved at the investigator's disposal simply by turning switches and potentiometers, or by feeding external command signals of desired wave forms.
Inhibition of fibrin-platelet interactions by fibrinogen-degradation fragment D
Authors: Orloff K. G. , Michaeli D.
Published: December 2017

Homogenized fibrin induced platelet aggregation and the release of serotonin from human platelets. Fragment D, purified from a plasmin digest of human fibrinogen, inhibited these platelet-fibrin interactions. Using a radiolabeled fragment D, it was possible to demonstrate saturable binding of fragment D to fibrin. Nonlabeled fragment D competed with the radiolabeled fragment D for binding to fibrin. Furthermore, the binding of fragment D to fibrin paralleled its ability to inhibit the fibrin-induced release of platelet serotonin. It is postulated that the inhibitory effect of fragment D on fibrin activation of platelets is due to the binding of fragment D to fibrin. The bound fragment D may cover up or block sites on fibrin that are involved in fibrin-platelet interactions. This would then result in inhibition of the fibrin-induced platelet aggregation and release of platelet serotonin.
Construction of a multipolar needle electrode for activation study of the heart
Authors: Kasell J. , Gallagher J. J.
Published: December 2017

The study of transmural activation of the intact heart requires placement of multipolar needle electrodes through the wall of the beating heart. This report describes a method developed for constructing lightweight multipolar needles with 10-30 leads mounted 1 mm apart. The electrodes are constructed from readily available materials and no special equipment is required. The electrodes are well suited to the intraoperative mapping studies required to surgically correct arrhythmias.
Stimulation of fibrinogen synthesis by thrombin in rabbits with ancrod-induced afibrinogenemia
Authors: Alving Barbara M. , Evatt Bruce L. , Bell William R.
Published: December 2017

The effect of intravenous infusions of thrombin on fibrinogen synthesis was evaluated in rabbits rendered afibrinogenemic by ancrod. Fibrinogen production and catabolism were measured simultaneously with 75Se-labeled selenomethionine (75SeM) and with 125I-labeled fibrinogen injected 5, 12, 18, or 26 h after ancrod. In normal rabbits the infusion of ancrod (2 U/kg body mass during 1 h) did not alter fibrinogen synthesis nor did it affect the rate of fibrinogen catabolism measured during a period of 5–120 h after ancrod administration. Normal rabbits that received purified bovine thrombin (100 U/kg body mass during 1 h) exhibited a twofold stimulation of fibrinogen synthesis as measured by the incorporation of 75SeM injected 5 h after thrombin. Rabbits made afibrinogenemic by infusion of ancrod 5 h before thrombin also showed a twofold increase in fibrinogen synthesis, as did animals that received ancrod immediately after thrombin. These experiments show that ancrod alone has no effect on fibrinogen production, and that thrombin stimulates fibrinogen synthesis in afibrinogenemic rabbits to the same extent as in controls

fibrinogen-fibrin degradation products; fibrinogen catabolism

Submitted on March 29, 1977