bluuebunny/crossref_metadata_2025 huggingface dataset:
Late preconditioning against stunning is not mediated by increased antioxidant defenses in conscious pigs
Authors: Tang Xian-Liang , Qiu Yumin , Turrens Julio F. , Sun Jian-Zhong , Bolli Roberto
Published: December 2017

Previous studies in conscious pigs have demonstrated that a sequence of ten 2-min coronary occlusion/2-min reperfusion cycles renders the heart relatively resistant to myocardial stunning 24 h later [late preconditioning (PC) against stunning] by an unknown mechanism. Since oxygen radicals contribute importantly to myocardial stunning and since antioxidant enzymes have been reported to be upregulated 24 h after PC in dogs and rabbits, we tested the hypothesis that late PC against stunning is related to an increase in endogenous antioxidant defenses. Chronically instrumented conscious pigs underwent a sequence of ten 2-min coronary occlusion/2-min reperfusion cycles (preconditioned group, n = 11) or received no intervention (control group, n = 5). Twenty-four hours later, pigs were killed and the myocardial levels of Mn superoxide dismutase (SOD), Cu-Zn SOD, catalase, glutathione (GSH) peroxidase, GSH reductase, GSH, GSH disulfide, α-tocopherol, and ascorbate were measured. There were no differences in any of the enzymatic or nonenzymatic antioxidants between the ischemic and nonischemic regions in the preconditioned group or between the control and the preconditioned group. Thus, when a marked protection against stunning was present (24 h after PC), no alteration in antioxidant defenses was observed. These results indicate that, in conscious pigs, late PC against myocardial stunning is not mediated by increased endogenous antioxidant defenses, thereby refuting one of the major current hypotheses regarding this phenomenon.
Autoreceptor-induced inhibition of neuropeptide Y release from PC-12 cells is mediated by Y2receptors
Authors: Chen Xiaoli , Dimaggio Debora A. , Han Song Ping , Westfall Thomas C.
Published: December 2017

Pheochromocytoma (PC)-12 cells express Y1, Y2, and Y3neuropeptide Y (NPY) receptors when differentiated with nerve growth factor (NGF). The present work evaluated NGF-differentiated PC-12 cells as a model system to study modulation of NPY release by NPY autoreceptors. We demonstrated that both K+and nicotine stimulated concomitant release of NPY and dopamine from differentiated PC-12 cells. We also showed in this study that NPY release from PC-12 cells was attenuated in a concentration-dependent manner by peptide YY (PYY)-(13—36), a selective agonist for the Y2type of NPY receptors. This result demonstrated that NPY release could be modulated by NPY autoreceptors of the Y2subtype. The inhibitory action of PYY-(13—36) may be mediated at least in part by inhibition of N-type Ca2+channels, because PYY-(13—36) could not produce further inhibitory effects in the presence of a maximum effective concentration of ω-conotoxin, an N-type Ca2+-channel blocker. The inhibition by PYY-(13—36) could be blocked by pretreatment of cells with pertussis toxin, suggesting that an inhibitory GTP-binding protein was involved. Furthermore, the function of NPY autoreceptors could be modulated by other receptors such as β-adrenergic and ATP receptors. The evoked release of NPY was also attenuated by ATP and adenosine, which have been shown to be colocalized and coreleased with NPY from sympathetic nerve terminals. These results suggest that PC-12 cells differentiated with NGF may be an ideal model to study regulatory mechanisms of NPY release and that autoreceptor-mediated regulation of NPY release appears to act through the Y2subtype of the NPY receptor.
Altered K+current of ventricular myocytes in rats with chronic myocardial infarction
Authors: Rozanski George J. , Xu Zhi , Zhang Kun , Patel Kaushik P.
Published: December 2017

The aim of the present study was to define the cellular mechanisms underlying changes in K+channel function in the failing heart after myocardial infarction. Rats with left coronary artery ligation were prepared and allowed to recover for 16 wk before study. Animals with chronic infarction exhibited marked cardiac hypertrophy and signs of heart failure, as indicated by a nearly twofold increase in heart weight- and lung weight-to-body weight ratios, respectively, compared with time-matched controls. Cardiac hypertrophy was also evident by a 49% increase in whole cell capacitance of isolated left ventricular myocytes ( P < 0.05). Voltage-clamp experiments revealed that the maximum density of the Ca2+-independent, transient outward current ( Ito), measured at +60 mV, was 42% less in myocytes from infarcted hearts than in myocytes from control hearts ( P < 0.05), whereas the inward rectifier current ( IK1) density was not different between groups. The reduced Itodensity in the infarcted group was reversed, however, in 4–5 h by treatment with exogenous dichloroacetate or pyruvate, both activators of pyruvate dehydrogenase. Moreover, control myocytes incubated for 6 h in the presence of an inhibitor of pyruvate dehydrogenase, 3-bromopyruvate, exhibited a concentration-dependent decrease in Itodensity compared with untreated cells. The present data demonstrate that Itodensity is reversibly decreased in surviving myocytes from infarcted hearts and suggest that mechanisms related to glucose metabolism via pyruvate dehydrogenase may be involved. These postinfarction changes in myocyte Itochannel function may relate to impaired contractility and arrhythmogenesis, which are characteristic of the intact, failing heart.
Mechanism of lidocaine block of late current in long Q-T mutant Na+ channels
Authors: Dumaine R. , Kirsch G. E.
Published: December 2017

Inherited long Q-T syndrome is a ventricular arrhythmia associated with delayed repolarization and the risk of sudden death. The chromosome 3-linked form of the disease (LQT3) is associated with mutations in the cardiac Na+ channel (N1325S or R1644H; or deletion of residues 1,505–1,507, ΔKPQ) that increase late inward currents and may cause delayed repolarization. Late currents arise from dispersed reopenings (N1325S and R1644H) or from reopenings combined with prolonged bursts (ΔKPQ). Therefore, we tested whether lidocaine blockade of late current varied among the different LQT3 mutant channels. We found that lidocaine preferentially blocked late over peak current and that the blockade was equally effective in all three channels, expressed in Xenopusoocytes. Lidocaine inhibited both dispersed reopenings and bursting in single channels without affecting mean open times. In the absence of drug, inactivating prepulses inhibited bursting but not dispersed reopenings. We suggest that lidocaine block of late current in LQT3 channels acts via a common mechanism involving stabilization of inactivation. Therefore, blockers that target the inactivated state may be effective therapeutic agents in all three biophysical phenotypes of LQT3.
Nitric oxide from neuronal NOS plays critical role in cerebral capillary flow response to hypoxia
Authors: Hudetz Antal G. , Shen Hui , Kampine John P.
Published: December 2017

We investigated, using a direct, intravital microscopic technique, whether nitric oxide (NO) from neuronal nitric oxide synthase (nNOS) plays a role in the cerebral capillary flow response to acute hypoxia. Erythrocyte flow in subsurface capillaries of the frontoparietal cortex of adult Sprague-Dawley rats was visualized using epifluorescence videomicroscopy after fluorescent labeling of red blood cells (RBC) in tracer concentrations. The velocity of labeled RBC in individual capillaries was measured off-line using an image analysis system. Hypoxia was produced by lowering the inspired O2 concentration to 15% for 5 min in control animals and in those pretreated with the selective nNOS inhibitor 7-nitroindazole (7-NI; 20 mg/kg ip). In the control group, hypoxia increased RBC velocity by 34 ± 8%. In the group treated with 7-NI, this response was reversed to a statistically significant 8 ± 3% decrease. This paradoxical response to hypoxia after 7-NI was observed in nearly all capillaries. 7-NI itself decreased the baseline RBC velocity by 12 ± 4%. The cerebral hyperemic response to hypoxia was also assessed with the laser Doppler flow (LDF) technique. In control animals, hypoxia produced a 33 ± 6% increase in LDF, similar to the increase in RBC velocity. After 7-NI treatment, the response to hypoxia was moderately attenuated but still significant at a 19 ± 2% increase in LDF. These results support the role of NO from nNOS in the cerebral hyperemic response to hypoxia. They imply that 7-NI interfered with a physiological mechanism that was fundamental to cerebral capillary flow regulation and provide direct evidence that cerebral capillary perfusion may be dissociated from a concurrent change in regional tissue perfusion as reflected by LDF. In conclusion, NO from nNOS contributes to the maintenance of RBC flow in cerebral capillaries and plays a critically important role in the selective regulation of cerebral capillary flow during hypoxia.
Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries
Authors: Geary Greg G. , Krause Diana N. , Duckles Sue P.
Published: December 2017

Gender differences in the incidence of stroke and migraine appear to be related to circulating levels of estrogen; however, the underlying mechanisms are not yet understood. Using resistance-sized arteries pressurized in vitro, we have found that myogenic tone of rat cerebral arteries differs between males and females. This difference appears to result from estrogen enhancement of endothelial nitric oxide (NO) production. Luminal diameter was measured in middle cerebral artery segments from males and from females that were either untreated, ovariectomized (Ovx), or ovariectomized with estrogen replacement (Ovx + Est). The maximal passive diameters (0 Ca2++ 1 mM EDTA) of arteries from all four groups were identical. In response to a series of 10-mmHg step increases in transmural pressure (20–80 mmHg), myogenic tone was greater and vascular distensibility less in arteries from males and Ovx females compared with arteries from either untreated or Ovx + Est females. In the presence of N G-nitro-l-arginine methyl ester (l-NAME; 1 μM), an NO synthase inhibitor, myogenic tone was increased in all arteries, but the differences among arteries from the various groups were abolished. Addition ofl-arginine (1 mM) in the presence of l-NAME restored the differences in myogenic tone, suggesting that estrogen works through an NO-dependent mechanism in cerebral arteries. To determine the target of NO-dependent modulation of myogenic tone, we used tetraethylammonium (TEA; 1 mM) to inhibit large-conductance, calcium-activated K+(BKCa) channels. In the presence of TEA, the myogenic tone of arteries from all groups increased significantly; however, myogenic tone in arteries from males and Ovx females remained significantly greater than in arteries from either untreated or Ovx + Est females. This suggests that activity of BKCa channels influences myogenic tone but does not directly mediate the effects of estrogen. Estrogen appears to alter myogenic tone by increasing cerebrovascular NO production and/or action.
Concept of a Common Protein Moiety, Containing Disulfide Bonds, in Prothrombin, Prothrombin Derivative (Autoprothrombin) and Thrombin
Authors: Carter John R. , Warner E. D.
Published: December 2017

With a recently devised argentometric amperometric method, disulfide was demonstrated in biothrombin, citrate thrombin and prothrombin derivative (autoprothrombin) in the same quantity (43 µm/100 mg N) as that present in prothrombin. Sulfhydryl groups were not detected in any of these clotting factors. Prolonged storage and denaturation by heating before disulfide could be detected in some samples of thrombin, as well as a difference in sensitivity to the inhibitory effect of sulfhydryl compounds, indicate a distinction between prothrombin and thrombin in the accessibility of their —S—S— bonds. The prothrombin derivative (autoprothrombin) on which the sulfhydryl and disulfide analyses were performed was shown to be deficient in prothrombin and thrombin activity, to exhibit pronounced factor VII activity and to be capable of conversion to thrombin by sodium citrate, but not by biological activators. The inhibition, amperometric and activator studies provide additional support for a monophyletic hypothesis of a single, but complex, glycoprotein, which possesses a protein moiety containing—S—S—bonds, and which by alteration of its side chains or end groups, may exhibit prothrombin, thrombin or accelerator activity. Such studies render the possibility that factor VII is a specific protein entity, increasingly doubtful.
Response to Stress by Riboflavin-Deficient and Pantothenic Acid-Deficient Dogs
Authors: Arnrich Lotte , Hurley Lucille S. , Forker Bluebell Reade , Morgan Agnes Fay
Published: December 2017

Normal, pantothenic acid-deficient and riboflavin-deficient young dogs were forced to swim for 25 minutes at 25°C and their blood glucose and in some cases blood lactic acid levels determined just before, just after and 1 and 2 hours after the test. A sharp rise in blood sugar level, markedly greater in the riboflavin-deficient dogs, occurred just after the swimming stress. An abnormal fall in level occurred in all deficient dogs after 2 hours. Severe under-feeding did not produce this change in a normal dog nor did force feeding alter it in riboflavin-deficient animals. Adrenocortical extract treatment diminished the poststress rise in normal and pantothenic acid-deficient but not in riboflavin-deficient dogs. Epinephrine treatment produced the same effects as swimming on blood sugar and lactic acid levels in normal animals. Adrenocortical extracts caused recovery from pantothenic acid-deficient hypoglycemic collapse but not from the similar riboflavin-deficient collapses. Thus increased sensitivity to insulin and to epinephrine appeared present in riboflavin deficiency and increased insulin sensitivity, normal response to epinephrine but hypocorticalism in pantothenic acid deficiency.
Effect of Bilateral Occlusion of Common Carotid Arteries on Cardiac Output and Oxygen Content of Arterial and Venous Blood in the Anesthetized Dog
Authors: Brind Shirley H. , Bianchine Joseph R. , Levy Matthew N.
Published: December 2017

Changes in cardiac output, mean arterial blood pressure, hematocrit ratio, and arterial and venous oxygen content resulting from bilateral carotid occlusion were investigated. Cardiac output exhibited no significant alteration during endosinusal hypotension, and the systemic hypertension engendered was attributed to an increase in vasomotor tone. Arterial and venous oxygen content, as well as hematocrit ratio, increased significantly during the period of carotid occlusion. This increase was ascribed to splenic contraction evoked by carotid occlusion, since no comparable augmentation was observed when the splenic circulation was temporarily interrupted.
Determination of Rates of Glucose Oxidation in Normal and Diabetic Dogs by a Technique Involving Continuous Injection of C14-Glucose
Authors: Searle G. L. , Strisower E. H. , Chaikoff I. L.
Published: December 2017

A procedure involving the continuous intravenous injection of C14-labeled glucose for measuring the rates of glucose oxidation and turnover in the dog is described. The total amount of labeled glucose administered during 6 hours need not exceed 0.1 mg, an amount quite negligible with respect to the size of the glucose pool in the dog and, consequently, too small to disturb the steady state of endogenous glucose metabolism. The advantage of this procedure lies in the fact that the calculations made are free of assumptions required in the single-injection method. As determined by the continuous-injection method, the normal dog oxidizes glucose at a rate of about 100 mg/kg/hr., and the diabetic dog (completely depancreatized) oxidizes glucose at a rate of about 50 mg/kg/hr. The injection of insulin in the diabetic dog restores the rates of glucose oxidation to near normal. A discussion is presented on the validity of the single-injection procedure for determination of rates of glucose oxidation in animals.
Nature of the Inhibition by Thiocyanate of the Iodide Concentrating Mechanism of the Thyroid Gland
Authors: Wollman Seymour H.
Published: December 2017

The dependence of the ratio of the radioiodide concentrations in thyroid gland and serum ( T/S) on the serum iodide concentration for fixed serum thiocyanate concentrations was investigated in C3H mice. The empirical equation (See PDF for Equation) where [SCN–] and [I–] are the serum thiocyanate and iodide concentrations in mg %, fitted the data within the limits of experimental error. Interpretation of the empirical equation was based on simple adsorption and active transport models of the iodide concentrating mechanism. The inhibition by thiocyanate of the thyroidal iodide concentrating mechanism appears to be competitive.
Energy Sources in the Bat
Authors: Dodgen C. L. , Blood F. R.
Published: December 2017

Early in the period of hibernation, the blood glucose of the bat was found to increase logarithmically with body temperature during dehibernation. Late in the period of hibernation, the blood glucose level increased with temperature but at a slower rate. Glycogen was shown to be a poor source of the energy required during dehibernation. The glycogen and lipid stores utilized by the bat during its hibernating period are sufficient to maintain the animal for 12 hours and 11 weeks, respectively, indicating the catabolism of other energy reserves. The utilization of protein in the hibernating bat is suggested by studies on blood urea nitrogen concentrations. Respiratory quotients of dehibernated animals indicate that materials other than lipids are catabolized after awakening, and the small stores of glycogen suggest protein as a component of the metabolic mixture.
Electrical Activity in Chick Amnion
Authors: Prosser C. Ladd , Rafferty Nancy S.
Published: December 2017

Isolated amnions from chick embryos showed spontaneous electrical activity, both local and conducted. Responses to barium and to shocks were conducted at an average of 2.9 cm/sec. (38–40°C). Conducted responses were observed in amnions at 5–10 days of incubation. Failure of conduction in older amnions appears related to the shortening and increased randomness of the muscle fibers. This preparation gives conclusive proof of conduction in nerve-free smooth muscle.
Whole Body and Tissue Inulin and Sucrose Spaces in the Rat
Authors: White H. L. , Rolf D.
Published: December 2017

Whole body inulin space in nephrectomized rats, calculated as found inulin/concentration in plasma water, rises exponentially with time, equalling water extractable Na space at about 15 hours, total body water at about 48 hours, and exceeding body volume at 68 hours. The rise is due to inulin stored in cells, cell entry proceeding at high complex rates in liver and spleen and at lower exponential rates in skin and skeletal muscle. Inulin space is initially lower than sucrose space, but rises faster. It overtakes sucrose at 9 hours and progressively exceeds it thereafter. The only meaningful expression of space in nephrectomized animals is obtained by taking plasma water level extrapolated to zero time. Nephrectomy 24 hours prior to inulin injection does not influence the results, indicating that cell permeability to inulin is not significantly changed after nephrectomy. The continuous infusion (with postinfusion recovery) method probably gives correct values in intact subjects because the intracellular inulin is not recovered during collection.
Effect of Quaternary Nitrogen Compounds on the S.A. Node in Profound Hypothermia
Authors: Cookson B. A. , DiPalma J. R.
Published: December 2017

Dogs anesthetized with sodium Pentothal and artificially respired with 100% oxygen characteristically go into a severe bradycardia when cooled to an average rectal temperature of 19°C. The onset of the severe bradycardia is usually quite abrupt (the ventricular rate dropping to a fifth of its former speed) and is associated with a change from sinus to nodal rhythm. This acute failure of sinus activity can be relieved by Q.N.C. injected i.v. The successful Q.N.C. are acetylcholine antagonists. These are either ganglionic blocking agents such as C.6., T.E.A., tetrabutylammonium iodide and WIN 2173 or neuromuscular blocking agents such as d-tubocurarine and Flaxedil. These drugs probably act directly on the sinus node. The unsuccessful Q.N.C. are either drugs such as thiamine whose ganglioplegic and curareform properties are weak or drugs such as choline and T.M.A. which mimic the action of acetylcholine. The restoration of sinus activity is frequently associated with ventricular extrasystoles and ventricular fibrillation. The drug with the lowest incidence of ventricular fibrillation is C.6, while WIN 2173 and T.E.A. have a high incidence.
Gastrointestinal Regulation of Water and Its Effect on Food Intake and Rate of Digestion
Authors: Lepkovsky Samuel , Lyman Richard , Fleming David , Nagumo Masako , Dimick Mildred M.
Published: December 2017

An investigation was undertaken to determine the effects of water deprivation during meals in rats. Food intake, gastrointestinal solids water content, rate of digestion and tissue water content were studied. Rats fed without water ate less food than rats fed with water. The gastric contents of all animals fed with or without water was approximately 49% water and indicates close regulation of water in the gastric contents. When fed without water, rats regulate their food intake so that it matches the amount of water that they can mobilize from their own tissues thereby maintaining the proper water:food ratio in the gastric contents. How this is reflected in the mechanisms that control food intake is unknown. The water found in the gastrointestinal contents of rats fed without water is furnished by selected tissues, especially the skin, probably the adipose tissues and perhaps other tissues. The contents of the intestinal lumen contains about 76% of water in all the rats irrespective of the availability of water with meals. The total solids in the intestinal lumen of the rats eating without water averaged 0.39 gm and 0.52 gm for the rats eating with water. The regulation of both water and solids in the intestinal lumen indicates that it acts as though it were a part of the internal environment. Withholding of water during meals does not appear to interfere with digestion but it definitely decreases appetite and effects a reduction of food intake.
Venous Blood Flow in the Dog Leg Following Cold Injury
Authors: Hardenbergh Esther , Bamberg Paul G.
Published: December 2017

In an attempt to determine the nature of the circulatory changes which occur in tissues injured by exposure to cold, the rate of venous outflow was studied in the dog's hind leg exposed to freezing temperatures. Before exposure to cold, control flow rates were determined, and changes in flow were measured following the injection of vasoactive drugs. Measurements were continued during a 30-minute immersion of the leg in an alcohol-solid carbon dioxide bath (app. –30°C), and then for several hours after the leg had been removed and thawed. Control blood flow rates were found to vary considerably from animal to animal (20 cc/min. to 90 cc/min.) but varied little in each individual. During exposure to cold, in most of the experiments, the legs froze: flow decreased almost to zero, and the temperature in the leg fell well below 0°C. In some experiments, however, the legs did not freeze: flow remained high throughout exposure, and tissue temperature remained above 0°C. In response to the injection of vasoactive drugs, the control venous outflow showed: a) a decrease after intravenous epinephrine; b) a decrease after intra-arterial epinephrine into the experimental leg; c) a transient increase after intra-arterial acetylcholine into the experimental leg. After exposure to cold, the legs which did not freeze still showed these reactions. However, in the legs which were frozen the reactions to intra-arterially injected drugs were very much diminished, and the flow was increased instead of decreased when epinephrine was intravenously administered.
Effects of Adrenocortical Steroids on the Propulsive Motility of Small Intestine
Authors: Streeten David H. P. , Hirschowitz Basil I. , Henley Keith S. , Pollard H. M.
Published: December 2017

Adrenal cortex extract in low concentrations (1:1400–1:250) increases the peristaltic contractions of small intestine and restores to fatigued intestinal segments normal peristaltic activity and the ability to propel fluid against a pressure gradient, in vitro (modified Trendelenburg technique). Adrenal cortex extract in high concentrations (1:150–1:25) reversibly inhibits or abolishes peristalsis in vitro. In adrenalectomized rats in vivo, adrenal cortex extract increases the rate of propulsion of dyes along the small intestine in moderate doses (1 ml b.i.d.), and decreases propulsion in large doses (5 ml b.i.d.). Cortisone, hydrocortisone and corticosterone in the amounts present in stimulant doses of adrenal cortex extract had no effect on intestinal propulsion, in vivo. Doses of aldosterone (0.1 and 0.5 µg b.i.d.) comparable with the amounts contained in the extract used and large doses of the electrolyte-controlling steroids, desoxycorticosterone (2.5 and 5 mg) and corticosterone (2.5 mg), reproduced the stimulant effects of the extract, in vivo. It is possible that the effects of aldosterone may be of significance in controlling intestinal motility under physiological and some pathological conditions.
Effect of Insulin on Utilization and Production of Circulating Glucose
Authors: Wall J. S. , Steele R. , de Bodo R. C. , Altszuler N.
Published: December 2017

C14 glucose was adminisered continuously to unanesthetized normal dogs by intravenous infusion following a priming dose at a rate which maintained the specific activity of the circulating glucose at a nearly constant level. Glucagon-free insulin was then administered intravenously in varying doses. Samples of blood were collected at intervals throughout the experiment and more frequently just subsequent to insulin injection. The glucose concentration of the circulating blood and the specific activity of this glucose, when considered together, allow calculations to be made of a) the outflow of glucose toward the tissue cells, and b) the inflow of glucose from the liver during the period after insulin injection. By this means it was shown that increased glucose uptake by the tissues is much more important than decreased delivery of glucose by the liver in bringing about insulin-induced hypoglycemia. It was also shown that recovery from hypoglycemia is brought about by increased glucose delivery by the liver and not by a decrease in tissue uptake of glucose below the preinsulin level. Alternative methods of calculation of absolute values for glucose inflow and outflow during periods of changing blood glucose concentrations are discussed and evaluated.
Certain Endocrine Aspects of the Anemia of Pregnancy in the Rabbit
Authors: Horger L. M. , Zarrow M. X.
Published: December 2017

The anemia of late pregnancy in the rabbit was found to be normochromic and normocytic and appeared to be due to a hemodilution since both the blood and plasma volume were increased. No significant change in the thiocyanate space was observed. A similar anemia was induced by treatment with 1 mg of extradiol daily except that an increase in the thiocyanate space was also noted. Progesterone alone had no effect, but modified the action of estradiol on blood and plasma volumes when administered in combination. The effect of estradiol was inhibited at a progesterone to estradiol ratio of 4:1, augmented at a ratio of 40:1, and unaltered at a ratio of 20:1. None of the combination treatments induced an anemia or a significant change in the thiocyanate space. It was concluded that although estrogen and progesterone may play important roles in the fluid metabolism of the pregnant female, they are not the sole etiologic agents in the anemia of pregnancy in the rabbit.
Effect of Hypertension on Arterial Wall Electrolytes During Desoxycorticosterone Administration
Authors: Tobian Louis , Redleaf Paul D.
Published: December 2017

Administration of desoxycorticosterone and NaCl resulted in an increased sodium and potassium content of the aorta in rats becoming severely hypertensive. Equivocally hypertensive animals on this regimen showed smaller increases in sodium and a decrease in potassium. Sodium restriction prevented both hypertension and changes in arterial wall chemistry from occurring in rats receiving desoxycorticosterone. Hypertension per se may be fundamentally associated with an increased potassium and sodium content in artery, as experimental renal hypertension is characterized by a similar electrolyte alteration.
Cation Shifts and Blood Pressure Regulation in the Dog
Authors: Friedman Sydney M. , Butt Robert M. , Friedman Constance L.
Published: December 2017

Dynamic transfers of sodium, potassium and water into and out of the extracellular space were studied in 13 dogs during induced changes in blood pressure. The inulin space, measured after a 2-hour equilibration period in the bilaterally nephrectomized animal, served as reference standard for the extracellular fluid. Infusions of norepinephrine, Pitressin and angiotonin were used as pressor, Isuprel and carbachol as depressor agents. In all instances, sodium, with variable amounts of water, moved out of the extracellular space during a rise in blood pressure and reversed during a fall. In general, potassium, in lesser bulk, moved inversely to sodium although it was more variable in degree and, in the case of angiotonin, did not change at all. These results accord with the theory that blood pressure regulation depends, inter alia, on the sodium transfer mechanisms.
Mechanics of Respiration in Unanesthetized Guinea Pigs
Authors: Amdur Mary O. , Mead Jere
Published: December 2017

A technique has been described by which tidal volume, intrapleural pressure and rate of flow of gas in and out of the respiratory system can be measured simultaneously in unanesthetized guinea pigs for periods of several hours. These data permit the calculation of the pulmonary flow-resistance and compliance for an experimental animal with normal reflex behavior. The values obtained on 200 normal and 20 tracheotomized animals for tidal volume, respiratory rate, minute volume, resistance and compliance are given.
Effects of a Body Cast on Aldosterone and Sodium Excretion in Dogs With Experimental Ascites
Authors: Davis James O. , Ball Wilmot C.
Published: December 2017

The effects of application of a plaster body cast upon aldosterone and sodium excretion were studied in eight dogs with experimental ascites. In association with an increase in intra-abdominal pressure, aldosterone output declined and sodium excretion increased. In three dogs net sodium loss occurred and in three animals the low sodium-potassium ratio of fecal electrolyte excretion characteristic of increased circulating aldosterone returned to normal. The increased sodium excretion was not attributable to elevated GFR as GFR was frequently unchanged or reduced. Furthermore, no consistent alterations in plasma sodium or potassium, T-1824 dye space in plasma or arterial pressure were detected. It is suggested that aldosterone secretion was decreased as a result of an increase in intra-abdominal pressure which inhibited filtration of fluid into the peritoneal cavity to form ascites.
Central Nystagmus Elicited by Stimulation of the Meso-Diencephalon in the Rabbit
Authors: Lachmann J. , Bergmann F. , Monnier M.
Published: December 2017

Unilateral stimulation at high frequencies (20–50 cps) of a circumscribed, meso-diencephalic area, including the reticular formation medial to the nucleus reticularis thalami and geniculate bodies in rabbit's brain, produces a ‘central nystagmus’ with its fast component usually directed towards the contralateral side. The reaction is tentatively explained as the result of a primary inhibition of the tonic innervation of the ipsilateral musculus rectus internus and of the contralateral rectus externus of the eyes. The relationship between this higher nystagmogenic area in the meso-diencephalon and the elementary three-neuron reflex arc of the nystagmus is discussed.
Effect of Hypothermia on Seizures Induced by Physical and Chemical Means
Authors: Owens Guy
Published: December 2017

Succinylcholine-immobilized adult cats had EEG-recorded seizure activity induced by a 60 cycle current of 8 milliamperes for 3 seconds, intravenous Metrazol (12 mg/ cat) and intravenous strychnine (2 mg/kg). Stigmatic electrodes were made at normal and ice bath induced low body temperatures. At 26–28°C electrically induced seizure activity could not be elicited using the same stimulus which at normal temperatures produced a continuous cortical discharge lasting from 2 to 4 minutes. The duration of EEG-recorded effects of the intravenously administered analeptic agents, however was greatly potentiated at 26–28°C. Metrazol-induced cortical discharges lasted for 18–20 minutes (responses at normal temperatures were inconsistent but lasted no longer than 8 sec.), and those produced by strychnine 90–100 minutes (at normal temperatures seizures persisted for about 10 min.).
Nonuniform Distribution of Vagal Effects on the Atrial Refractory Period
Authors: Alessi R. , Nusynowitz M. , Abildskov J. A. , Moe G. K.
Published: December 2017

The refractory period (RP) was measured at several points on the right atrial surface in anesthetized dogs. Under control conditions with vagi cut the values recorded at various points varied by no more than 40 msec. During stimulation of the vagus nerves, singly or together, the RP varied widely. At some points marked effects were observed, while at others little or no effect was apparent. Reflex excitation of the vagi, induced by increased arterial pressure, yielded similar results. It was concluded that the effects of vagal stimulation are not uniformly distributed.
Oxygen Pressure in Urine and Its Relation to Intrarenal Blood Flow
Authors: Rennie D. W. , Reeves R. B. , Pappenheimer J. R.
Published: December 2017

Oxygen tensions in renal pelvic urine, renal venous blood and arterial blood ( Pu, Pv, Pa) were measured in anesthetized dogs breathing oxygen tensions of 150, 760 and 1900 mm Hg. In dogs having high Diodrast extraction ratios, the respective values for Pu were 27, S.E. ± 3; 49 ± 5 and 120 ± 7 mm Hg. Corresponding values for Pv were 50 ± 3, 96 ± 8 and 858 ± 47 mm Hg. Renal O2 consumption was unaffected by oxygen tension; therefore, the increasing Pv– Pu cannot be interpreted as a gradient across tubule cells. In dogs having low Diodrast extraction ratios, Pu was higher (e.g. 72 ± 6 mm Hg in contrast to 49 ± 5 at 1 atm. O2). These results, which are difficult to explain by classical renal hemodynamics, can be accounted for by the cell-separation theory. Assuming that urine oxygen is equilibrated with peritubular capillary blood it is possible to calculate peritubular relative to arterial hematocrit ( HT/ Ha). HT/ Ha, so calculated, averages 0.52 ± .06 for high extraction kidneys and 0.96 ± .06 for low extraction kidneys, thus relating low Diodrast extraction to failure of cell-separation. An alternative mechanism, involving equilibration of urine oxygen with medullary, rather than peritubular, blood could also explain the facts provided that the hematocrit of medullary blood is low. Further work is required to localize the region of low oxygen tension within the kidney: the present results indicate, however, that the region concerned is supplied with blood of low red cell concentration. Oxygen in human bladder urine is largely determined by gaseous equilibration with ureteral walls and cannot be used as a measure of intrarenal oxygen pressure.
Slowly Changing Bioelectric Potentials Associated With the Blood-Brain Barrier
Authors: Tschirgi Robert D. , Taylor J. Langdon
Published: December 2017

A slowly changing bioelectric potential difference (P.D.) is measured in rats, rabbits, cats and dogs between various regions of the central nervous system (CNS) and the blood within the jugular vein. It is shown that the CNS-blood P.D. is very sensitive to alterations in alveolar CO2 tension, but this relationship is dependent upon the H+ concentration rather than CO2 per se. Whereas increasing intravenous H+ concentration increases CNS positivity, topical application of acid solutions directly to the cerebral cortex decreases CNS positivity. The same relationship is found for intravenous and topical K+. Anoxia and circulatory failure produce CNS negative deflections, often exceeding 15 mv, which do not return to zero for over 24 hours after death. Simultaneous measurements of arterial blood pH, cerebral cortex pH and CNS-blood P.D. reveal the following relationship among these variables: ΔP.D. = κ Δ log10 [H+]a/[H+]i where [H+]a is the H+ concentration of the arterial blood and [H+]i is the H+ concentration of the CNS interstitial fluid. For the CNS-blood P.D. between cerebral cortex and jugular blood of rabbits and rats, κ is found to be 29 ± 5. These results are interpreted as indicating a source of emf across the pan-vascular blood-brain barrier which resembles a membrane diffusion potential. The blood-brain barrier is postulated to be more permeable to H+ and K+ than to anions and other cations.
Effects of CO2, Bicarbonate and pH on the Performance of Isolated Perfused Guinea Pig Hearts
Authors: McElroy William T. , Gerdes Arthur J. , Brown E. B.
Published: December 2017

Guinea pig hearts were perfused with a balanced ion solution in which the pH was altered either by changing the CO2 tension of the gas in equilibrium with the solution or by varying the bicarbonate concentration of the solution. Heart rates, contraction amplitudes, and coronary flow rates were affected by changes in pCO2 or HCO3– concentration of the perfusing solution only when a change in pH resulted. Increasing the acidity produced a decrease in heart rate and contraction amplitude and an increase in coronary flow. High levels of bicarbonate (50 mm/l.) were sometimes slightly depressant to the heart even when pH was held constant.
Effect of Hypoxia on Cardiac Oxygen Consumption and Coronary Flow
Authors: Feinberg H. , Gerola A. , Katz L. N.
Published: December 2017

The arterial O2 content was gradually decreased in the anesthetized open-chested dog, prepared for total coronary flow measurement, while cardiac performance and myocardial O2 consumption were explored over a wide range. The coronary venous O2 content and the coronary arteriovenous O2 difference decreased in proportion to the decline in arterial O2, hence the percentage of myocardial O2 extracted remained relatively constant. The a-v O2 difference and the percentage of O2 extraction remained fairly constant at each level of arterial O2 over a wide range of cardiac performance and O2 consumption. Coronary blood flow increased both when the a-v O2 decreased and when the O2 consumption increased. The coronary flow response to hypoxia was commensurate with the decreased a-v O2—hence the O2 consumption/O2 availability ratio remained normal and constant throughout the period of hypoxemia. The O2 cost of cardiac external useful work (external efficiency) was essentially unchanged, while the O2 cost of cardiac effort, as measured by the product of blood pressure and heart rate, was only slightly altered by hypoxia.
Metabolism and electrical activity of the heart: action of 2–4-dinitrophenol and ATP
Authors: de Mello Walmor Carlos
Published: December 2017

The effects of DNP on the electrical activity of single cells of the sinus node, right auricle and A-V node, were studied with microelectrodes. It was observed that this agent caused an initial tachycardia followed by a bradycardia, a decrease in the duration of the action potential, a decrease of the resting potential and a decrease in the slope of diastolic depolarization of pacemaker tissues. A complete inhibition of the electrical activity was observed in 45 minutes after the addition of DNP to the perfusion fluid. A similar result was obtained with sodium azide. A significant recovery of the electrical activity was obtained with the use of a system with DNP and ATP. A possible increase of the extracellular potassium concentration produced by DNP similar to that observed in skeletal muscle is discussed. An incomplete loss of the resting potential observed with DNP makes it probable that at least a fraction of the resting potential is independent of the energy supplied by oxidative phosphorylation.
Myocardial oxygen consumption and coronary blood flow in hypothermia
Authors: Gerola A. , Feinberg H. , Katz L. N.
Published: December 2017

Effects of hypothermia (at 32° and 27°C) were determined in the open-chest anesthetized dog prepared for measurement of total coronary flow and myocardial oxygen consumption. When hypothermia was induced at any fixed cardiac output, cardiac oxygen consumption and heart rate declined while blood pressure remained constant. Cardiac external mechanical efficiency increased at the same time. Hypothermia did not alter the relationship between the myocardial oxygen requirement and the total cardiac effort as indicated by the product of blood pressure times heart rate. Without regard to the large individual variability, the coronary venous O2 rose; thus the general trend during the induction of hypothermia was a decline in the coronary A-V oxygen difference, the percentage O2 extracted by the heart and the ratio: cardiac O2 consumption/O2 availability. The coronary venous O2 content and the coronary A-V O2 difference remained fairly constant as the cardiac effort and its oxygen requirement varied during hypothermia, just as in the control period. Thus coronary flow was the only means of adjusting to the altered cardiac oxygen need in both periods.
Diffusion of oxygen from arterial to venous segments of renal capillaries
Authors: Levy Matthew N. , Sauceda Gerardo
Published: December 2017

Injections of three types of blood preparations were made into the renal arteries of dogs, namely, a) blood equilibrated with 95% O2, 5% CO2, b) arterial blood containing some methemoglobin-labeled erythrocytes and c) blood containing methemoglobinemic cells, but equilibrated with 95% O2, 5% CO2. The initial appearance time in the renal vein was 1.25 ± 0.97 second earlier for oxygen than for the methemoglobinemic red cells. When preparation c was introduced into the renal artery, a diphasic curve was consistently registered from the renal venous blood. The initial deflection was uniformly upright, indicating a preponderant effect due to increased oxygen saturation. This was followed by an inverted deflection, resulting from the predominant effect of methemoglobin. These findings are interpreted to indicate diffusion of some of the oxygen from arterial to venous limbs of capillary loops, probably the vasa recta located in the renal medulla.
Effect of temperature on function of isolated dog kidney
Authors: Harvey Rodney B.
Published: December 2017

The effects of cooling on an isolated dog kidney were studied using a heparinized dog as a source of arterial blood. Blood flow, O2 consumption, CO2 production and the excretion of inulin, creatinine, PAH, Na and K by this preparation were measured. Cooling was found to reduce blood flow and gaseous metabolism. Urine concentrations of tested substances approached plasma concentrations. These changes were reversed on warming. The net movement of PAH into the tubule was found to be highly sensitive to cooling. This indicates that the rate limiting reactions involved have high energy characteristics. H2O and Na net movements were more resistant to cooling. Glomerular filtration rate showed the least change with cooling. The net movement of Na out of the tubule and the concentration gradient opposing this movement do not remain proportional during cooling. It is also suggested that there may be some residual active transport of water and other substances at temperatures below 15°C.
Immediate variations in pulse wave velocity caused by Adrenalin in short, uniform parts of the arterial tree
Authors: Kraner James C. , Ogden Eric , McPherson Richard C.
Published: December 2017

Pulse wave velocity measurements confined to a 6–9-cm segment of the femoral artery in eight anesthetized dogs gave an average value of 7.8 m/sec. The velocity varies with the diastolic blood pressure. This was particularly noticeable in one dog which showed marked spontaneous variations of diastolic blood pressure from beat to beat. The response to Adrenalin was diphasic showing first an increase in pulse wave velocity and then a marked decrease without a corresponding decrease in diastolic blood pressure. This observation suggests a physical change in the artery compatible with relaxation of the smooth muscle, rather than contraction.
Central nystagmus. III. Functional correlations of mesodiencephalic nystagmogenic center
Authors: Bergmann F. , Lachmann J. , Monnier M. , Krupp P.
Published: December 2017

Transverse cuts at various levels of the rabbit brain stem have different effects on vestibular nystagmus and on central nystagmus elicited by electrical stimulation of the mesodiencephalic nystagmogenic area. While transections rostral to the sensitive region enhance both, probably by elimination of inhibitory influences from cortex or retina, transections caudal to this region, but rostral to the colliculi, abolish central nystagmus only. Transections at the level of the inferior colliculus abolish vestibular nystagmus only, while intermediate cuts may eliminate either response. When central nystagmus alone survives, its character is changed in a specific way indicating the important role of the vestibular nuclei in normal central nystagmus. These observations lead to an approximate localization of the common substrate for conjugate eye movements involved both in central and vestibular nystagmus. Longitudinal cuts through the posterior commissure provoke a temporary disconjugated nystagmus not described hitherto.
Role of fenestrated basement membrane in lymphatic absorption from peritoneal cavity
Authors: Allen Lane , Weatherford Tim
Published: December 2017

Polystyrene spheres with a range from chylomicron size up to 30 µ were injected into the peritoneal cavity of mouse, rat and cat, and were recovered from the regional lymph nodes. The largest recovered spheres in the mouse were 16.8 µ in diameter, in the rat and cat 24 µ. Inspection of the entire population of spheres recovered from lymph nodes 48 hours after intraperitoneal injection indicated that most of the fenestrations in the subperitoneal basement membrane are less than 5 µ in the mouse, and more than 5 µ in the cat. Fenestrations in the rat are intermediate between mouse and cat. The deductions as to fenestrations from inspection of the absorbed sphere populations is fairly well in accord with the histological picture in the mouse and cat. Many spheres reach the circulation and the larger ones are filtered out in the lungs, with resulting atelectasis.
Synthesis of creatine in nephrectomized rats
Authors: Goldman Ralph , Moss John X.
Published: December 2017

Glycocyamine, the creatine precursor, is reportedly synthesized in the kidney. Nephrectomized rats, kept alive by peritoneal dialysis for periods up to 17 days, showed a slight initial increase in total body and muscle creatine concentration, followed after 10 days by a slight decrease. The failure to observe the anticipated loss in creatine concentration after nephrectomy may be due to extrarenal glycocyamine synthesis, conservation of creatine released by catabolized tissue with loss in body weight, or reduced creatine breakdown. Nephrectomized rats were found to convert 6–20% as much C14-labeled glycine to creatine as unoperated controls. Ureter-ligated rats converted 35% of the control amount of glycine to creatine. Sham-operated rats produced essentially normal amounts of creatine. These data indicate that there is a nonrenal pathway of creatine synthesis which can produce 20% of the normal requirement. Other data suggest that 40–60% of creatine synthesis may be by extrarenal routes.