bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of halothane on [Ca2+]i transient, SR Ca2+ content, and force in intact rat heart trabeculae
Authors: Jiang Yandong , Julian Fred J.
Published: December 2017

The goal of this study was to test whether the well-known cardiodepressant effect of halothane is caused mainly by depression of the transient increase in intracellular Ca2+ concentration ([Ca2+]i) during a twitch. Intact rat ventricular trabeculae, paced at 0.5 Hz and 30°C with a bathing extracellular Ca2+ concentration ([Ca2+]o) of 2 mM, were used. The [Ca2+]iwas monitored with the use of fura 2 injected into the myoplasm. The sarcoplasmic reticulum (SR) Ca2+content was estimated with the use of rapid cooling (RC)-induced contracture force and Ca2+release. The relationship of the peak [Ca2+]itransient versus peak twitch force obtained with halothane is intermediate between those obtained with lowered [Ca2+]oand varying doses of 2,3-butanedione monoxime. The data indicate that the negative inotropic action of halothane at low (0.18 mM) dose is mainly achieved by reduction in the Ca2+ sensitivity of the contractile apparatus, whereas, at high dose (0.55 mM), halothane acts both by reducing the [Ca2+]itransient and the Ca2+ sensitivity of the contractile system. At moderate (0.37 mM) dose, the effects were midway between low and high doses. With the use of RC contracture force alone, the reduction of SR Ca2+content caused by halothane is overestimated.
Muscle blood f low at onset of dynamic exercise in humans
Authors: Rådegran G. , Saltin B.
Published: December 2017

To evaluate the temporal relationship between blood flow, blood pressure, and muscle contractions, we continuously measured femoral arterial inflow with ultrasound Doppler at onset of passive exercise and voluntary, one-legged, dynamic knee-extensor exercise in humans. Blood velocity and inflow increased ( P < 0.006) with the first relaxation of passive and voluntary exercise, whereas the arterial-venous pressure difference was unaltered [ P = not significant (NS)]. During steady-state exercise, and with arterial pressure as a superimposed influence, blood velocity was affected by the muscle pump, peaking ( P < 0.001) at ∼2.5 ± 0.3 m/s as the relaxation coincided with peak systolic arterial blood pressure; blood velocity decreased ( P < 0.001) to 44.2 ± 8.6 and 28.5 ± 5.5% of peak velocity at the second dicrotic and diastolic blood pressure notches, respectively. Mechanical hindrance occurred ( P < 0.001) during the contraction phase at blood pressures less than or equal to that at the second dicrotic notch. The increase in blood flow (Q˙) was characterized by a one-component (∼15% of peak power output), two-component (∼40–70% of peak power output), or three-component exponential model (≥75% of peak power output), whereQ˙( t) =Q˙passive+ ΔQ˙1⋅ [1 − e−( t− TD1/τ1)] + ΔQ˙2⋅ [1 − e−( t − TD2/τ2)] + ΔQ˙3⋅ [1 − e−( t − TD3/τ3)]; Q˙passive, the blood flow during passive leg movement, equals 1.17 ± 0.11 l/min; TD is the onset latency; τ is the time constant; ΔQ˙ is the magnitude of blood flow rise; and subscripts 1–3 refer to the first, second, and third components of the exponential model, respectively. The time to reach 50% of the difference between passive and voluntary asymptotic blood flow was ∼2.2–8.9 s. The blood flow leveled off after ∼10–150 s, related to the power outputs. It is concluded that the elevation in blood flow with the first duty cycle(s) is due to muscle mechanical factors, but vasodilators initiate a more potent amplification within the second to fourth contraction.
Patterns of excitation-contraction coupling in arterioles: dependence on time and concentration
Authors: Xia J. , Duling B. R.
Published: December 2017

We sought to understand the excitation-contraction coupling process in arterioles. KCl or phenylephrine (PE) was applied via the superfusion solution or by brief pulsatile ejections from a micropipette onto unpressurized arterioles (in vitro) from either the guinea pig small intestine or hamster cheek pouch. With either mode of application, KCl caused depolarizations that were tightly and predictably correlated with subsequent constrictions (electromechanical coupling). In contrast, the relationship between membrane potential and vasoconstriction in response to phenylephrine was dependent on both stimulus duration and agonist concentration. Application of short pulses of PE (<1 s) produced mechanical responses that were dominated by pharmacomechanical coupling (i.e., they were not associated with changes in membrane potential). With longer PE stimuli, electromechanical coupling became more important and dominated microvessel responses. We conclude that adequate understanding of the signaling process in microvessels requires a consideration of both concentration and duration of application. Both the mode and duration of agonist application affect the relative degree of electromechanical or pharmacomechanical coupling in response to a vasomotor stimulus. These observations have important implications for intracellular and intercellular signaling.
Dynamic transduction properties of in situ baroreceptors of rabbit aortic depressor nerve
Authors: Sato Takayuki , Kawada Toru , Shishido Toshiaki , Miyano Hiroshi , Inagaki Masashi , Miyashita Hiroshi , Sugimachi Masaru , Knuepfer Mark M. , Sunagawa Kenji
Published: December 2017

We developed a new method for isolating in situ baroreceptor regions of the rabbit aortic depressor nerve (ADN) and estimated the transfer function from pressure to afferent nerve activity in the frequency range of 0.01–5 Hz by a white noise technique. Complete isolation of the baroreceptor area of the right ADN was made in situ by ligation of the innominate artery and the right subclavian and common carotid arteries. We altered the pressure in the isolated baroreceptor area according to a binary quasi-white noise between 80 and 100 mmHg in 12 urethan-anesthetized rabbits. The gain increased two to three times as the frequency of pressure perturbation increased from 0.01 to 2 Hz and then decreased at higher frequencies. The phase slightly led below 0.2 Hz. The squared coherence value was >0.8 in the frequency range of 0.01–4 Hz. The step responses estimated from the transfer function were indistinguishable from those actually observed. We conclude that the baroreceptor transduction of the ADN is governed by linear dynamics under the physiological operating pressure range.
Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo
Authors: Devlin Alison M. , Brosnan M. Julia , Graham Delyth , Morton James J. , McPhaden Allan R. , McIntyre Martin , Hamilton Carlene A. , Reid John L. , Dominiczak Anna F.
Published: December 2017

To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with N G-nitro-l-arginine methyl ester (l-NAME; 10 mg ⋅ kg−1 ⋅ day−1).l-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) froml-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings froml-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed thatl-NAME treatment caused reexpression of the fetal skeletal α-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.
Capillaries demonstrate changes in membrane potential in response to pharmacological stimuli
Authors: McGahren Eugene D. , Beach James M. , Duling Brian R.
Published: December 2017

It has been proposed that capillaries can detect changes in tissue metabolites and generate signals that are communicated upstream to resistance vessels. The mechanism for this communication may involve changes in capillary endothelial cell membrane potentials which are then conducted to upstream arterioles. We have tested the capacity of capillary endothelial cells in vivo to respond to pharmacological stimuli. In a hamster cheek pouch preparation, capillary endothelial cells were labeled with the voltage-sensitive dye di-8-ANEPPS. Fluorescence from capillary segments (75–150 μm long) was excited at 475 nm and recorded at 560 and 620 nm with a dual-wavelength photomultiplier system. KCl was applied using pressure injection, and acetylcholine (ACh) and phenylephrine (PE) were applied iontophoretically to these capillaries. Changes in the ratio of the fluorescence emission at two emission wavelengths were used to estimate changes in the capillary endothelial membrane potential. Application of KCl resulted in depolarization, whereas application of the vehicle did not. Application of ACh and PE resulted in hyperpolarization and depolarization, respectively. The capillary responses could be blocked by including a receptor antagonist (atropine or prazosin, respectively) in the superfusate. We conclude that the capillary membrane potential is capable of responding to pharmacological stimuli. We hypothesize that capillaries can respond to changes in the milieu of surrounding tissue via changes in endothelial membrane potential.
Ischemic preconditioning: antiarrhythmic effects and electrophysiological mechanisms in isolated ventricle
Authors: Zhu Jiequan , Ferrier Gregory R.
Published: December 2017

The objective of this study was to identify cellular electrophysiological mechanisms by which ischemic preconditioning decreases arrhythmias in an isolated ventricular tissue model of ischemia and reperfusion. Electrical activity was recorded with microelectrodes from endocardium and epicardium of paced guinea pig right ventricular free walls. Control preparations were exposed for 15 min to Tyrode solution modified to simulate selected ischemic conditions and then were reperfused for 30 min with normal solution. Preconditioned tissues were exposed to a 2- or 5-min period of simulated ischemia before this same protocol. Neither preconditioning protocol affected incidence of ventricular tachycardia (VT) in ischemia; however, the 5-min protocol significantly decreased premature beats (PVB) and transmural conduction block. Preconditioning for 5 min, but not 2 min, significantly decreased reperfusion-induced VT and PVB. Ischemic preconditioning did not change effects of ischemia or reperfusion on action potential duration, effective refractory period, or endocardial conduction time. However, preconditioning markedly attenuated depression of transmural conduction by ischemia and early reperfusion and thereby prevented conduction delays necessary for transmural reentry.
Dissociation between volume blood flow and laser-Doppler signal from rat muscle during changes in vascular tone
Authors: Kuznetsova Larisa V. , Tomasek Nicole , Sigurdsson Gisli H. , Banic Andrej , Erni Dominique , Wheatley Anthony M.
Published: December 2017

Although the laser-Doppler flowmetry (LDF) signal from skeletal muscle has been shown to provide a good measure of blood flow under some conditions, its behavior during administration of vasoactive substances has never been addressed. The aims of this study were to compare 1) changes in LDF signal with those in total muscle blood flow measured with radioactive microspheres after ganglionic blockade (chlorisondamine) and during administration of angiotensin II (ANG II), phenylephrine (PE), and isoproterenol (Iso) and 2) changes in vascular resistance estimated by the two techniques. The LDF signal from the biceps femoris muscle was investigated in anesthetized male Wistar rats. Ganglionic blockade led to a significant ( P < 0.05) fall in mean arterial pressure (MAP) [medians (lower, upper quartiles): 78 (72, 83) vs. 127 (114, 138) mmHg under basal conditions], muscle blood flow (MBF, microsphere technique; 61%), and the LDF signal (29%). Muscle vascular resistance (MVR = MAP/MBF) was increased (64%, P < 0.05), but vascular resistance estimated as MAP/LDF signal (MVRLDF) was unchanged. During ANG II and PE infusions, MAP rose ( P< 0.05) to 178 (155, 194) and 127 (124, 142) mmHg, respectively; MBF did not change compared with the preinfusion (postganglionic blockade) level and remained significantly ( P< 0.05) lower than baseline, whereas the LDF signal increased up to a level not different from baseline. MVR rose and was significantly ( P < 0.05) higher than baseline, whereas MVRLDF did not differ significantly from baseline. During Iso infusion, MAP fell [58 (56, 60) vs. 94 (92, 102) mmHg, P < 0.05], the LDF signal was reduced (49%, P < 0.05) despite a large increase in MBF (139%, P < 0.05), and MVR fell (74%, P < 0.05), whereas MVRLDF did not change vs. preinfusion level. Our results suggest that 1) changes in the LDF signal from muscle may not correlate with changes in total muscle blood flow measured by the microsphere technique during infusion of vasoactive substances and 2) the use of LDF data for estimation of MVR during changes in vascular tone in rat skeletal muscle is probably not appropriate.
Localization of preproenkephalin mRNA in rat heart: selective gene expression in left ventricular myocardium
Authors: Weil Joachim , Eschenhagen Thomas , Fleige Gerrit , Mittmann Clemens , Orthey Ellen , Scholz Hasso
Published: December 2017

The enkephalins are derived from a common precursor protein known as preproenkephalin (ppENK). Enkephalins appear to be one of the endogenous ligands for the opiate receptors. In the rat the ventricular myocardium contains more ppENK mRNA than any other tissue. To gain further insight into the role of cardiac enkephalins, the regional and developmental distribution of ppENK mRNA was studied by Northern blotting and in situ hybridization. In the early postnatal period, ppENK mRNA is low in atrial and ventricular myocardium. With maturation, ppENK expression increases threefold in left and right ventricular tissue, but not in the atria or cardiac conductive system. Interestingly, ppENK mRNA levels are four times higher in the left than in the right chamber. Thus, to our knowledge, ppENK is the only gene exhibiting marked differences in expression between the adult right and left ventricle. Given the left-side preference of ppENK expression, the possibility is raised that the left ventricle is an endocrine organ that supplies the body with enkephalins.
Alterations in small arterioles precede changes in limb skeletal muscle after myocardial infarction
Authors: Thomas D. Paul , Hudlicka Olga , Brown Margaret D. , Deveci Durmus
Published: December 2017

We tested the hypothesis that alterations in arterioles in locomotor skeletal muscles in rats with myocardial infarction (MI), but before development of congestive heart failure (CHF), precede structural and functional changes commonly observed in limb muscle in association with CHF. Resting diameters of third- (A3) and fourth-order arterioles (A4) in extensor digitorum longus (EDL) muscle were significantly smaller in rats with nonfailing small and medium-sized MI compared with control animals. Dilation of A4 in response to 10−4 M adenosine was significantly attenuated in both groups ( P < 0.05), whereas dilation of A3 was unaltered. Microvessels from both groups of infarcted rats constricted to all doses of acetylcholine (10−9, 10−8, and 10−7 M) and showed a significantly exaggerated vasoconstrictor response to norepinephrine (10−9, 10−8, and 10−7 M) compared with microvessels in control rats ( P < 0.05). Peak isometric tension of combined tibialis anterior and EDL muscles and muscle fatigue (final/peak tension × 100), measured during 5-min isometric supramaximal twitch contractions at 4 Hz, were similar in control and MI rats (218 ± 7 vs. 213 ± 15 g/g muscle and 52 ± 1 vs. 51 ± 9%, respectively; n = 5 for both). There was also no difference with respect to the proportion of oxidative fibers or capillary-to-fiber ratios. Our results indicate that, in rats with left ventricular dysfunction but without failure, decreased diameter and perturbations in reactivity of small arterioles precede alterations in skeletal muscle performance often seen at a later date in association with CHF. These findings are consistent with the notion of aberrant endothelial and smooth muscle function and may contribute to the maintenance of blood pressure after MI but before CHF.
Systemic and uterine blood flow distribution during prolonged infusion of 17β-estradiol
Authors: Magness Ronald R. , Phernetton Terrance M. , Zheng Jing
Published: December 2017

Prolonged 17β-estradiol (E2β) infusion decreases mean arterial pressure (MAP) and systemic vascular resistance (SVR) while increasing heart rate (HR) and cardiac output (CO). It is unclear, however, which systemic vascular beds show increases in perfusion. The purpose of this study was to determine which reproductive and nonreproductive vascular beds exhibit alterations in vascular resistance and blood flow during prolonged E2β infusion. Nonpregnant, ovariectomized sheep received either vehicle ( n = 6) or E2β (5 μg/kg iv bolus followed by 6 μg/kg over 24 h for 10 days; n= 9), and blood flow distribution was evaluated using radiolabeled microspheres at control and 120 min and 3, 6, 8, and 10 days of infusion. During E2β infusion MAP (87 ± 5 mmHg; mean ± SE) decreased 3–9% and HR (83 ± 5 beats/min) increased 4–31%. The combined baseline (control) perfusion to the uterus, broad ligament, oviducts, cervix, vagina, and mammary gland (reproductive blood flows) was 49 ± 9 ml/min; at 120 min, E2β increased flow ( P < 0.001) to 605 ± 74 ml/min (1,263%) and it remained elevated, but at a reduced rate, on day 3 (218 ± 44 ml/min; 399%), day 6 (144 ± 23; 217%), day 8(181 ± 19; 321%), and day 10 (204 ± 48; 454%), accounting for only 3–17% of the E2β-induced increase in CO. During this E2β treatment, there also were significant decreases in vascular resistances leading to increases ( P < 0.05) in blood flows to several nonreproductive (systemic) vascular beds including skin (32–113%), coronary (32–190%), skeletal muscle (25–133%), brain (21–292%), bladder (128–524%), spleen (87–180%), and pancreas (35–137%) vascular beds. Responses of these combined nonreproductive blood flows represent the major percentage (21–67%) of the E2β-induced increase in CO. Vehicle infusion was without effect. We conclude that prolonged E2β infusion increases reproductive and nonreproductive tissue blood flows. The latter appears to principally be responsible for the observed rise in CO and decrease in SVR.
Ionic diffusion in transverse tubules of cardiac ventricular myocytes
Authors: Shepherd Neal , McDonough Holly B.
Published: December 2017

We have estimated the rate of diffusion of calcium ions in the transverse tubules of isolated cardiocytes by recording changes in peak calcium current ( I Ca) caused by rapid changes of the extracellular calcium concentration ([Ca]o) at various intervals just preceding activation of I Ca. Isolated ventricular cells of guinea pig heart and atrial cells from rabbit heart were voltage-clamped (whole cell patch), superfused at a high flow rate, and stimulated continuously with depolarizing pulses (0.5 Hz, 200- or 20-ms pulses from a holding potential of −45 or −75 mV to 0 mV). In ventricular cells, the change in peak I Ca following a sudden change of [Ca]oincreased rapidly as the delay between the solution change and depolarization was increased, up to a delay of ∼75 ms [time constant (τ) ≈ 20 ms, 30–40% of total current change), and then increased more slowly (τ ≈ 200 ms, 60–70% of total current change); 400–500 ms were needed to achieve 90% of the total current increase. In atrial cells, a clear separation into two phases was not possible and 90% of the current change occurred within 85 ms. The slow phase of current change, which was unique to the ventricular cells, presumably reflects the slow equilibration of ions between the bulk perfusate and the lumina of the transverse tubules. If the lengths of the transverse tubules were equal to the cell thickness, the slow rate of change of current would be consistent with an apparent diffusion coefficient for calcium ions of 0.95 × 10−6cm2/s, considerably smaller than the value in bulk solution (7.9 × 10−6cm2/s). Most likely, this discrepancy is due to a high degree of tortuosity in the transverse tubular system in guinea pig ventricular cells or possibly to ion binding sites within the tubular membranes and glycocalyx.
Sulfhydryl Groups and Gastric Acid Secretion
Authors: Davenport Horace W. , Chavré Virginia J. , Davenport Virginia D.
Published: December 2017

Gastric acid secretion is inhibited by reagents attacking sulfhydryl groups: iodoacetate amide (IAAm), N-ethyl maleimide (NEM), p-chloromercuribenzoate (ClHgB) and various forms of trivalent arsenic. An attempt was made to discover the nature of the group attacked by studying the effect of these and other reagents upon four sulfhydryl systems of the stomach: succinoxidase, glutathione (GSH), coenzyme A (CoA) and lipoic acid. Succinoxidase activity is reduced only slightly by treatment with IAAm or NEM which severely inhibits secretion. Both the enzyme system and secretion are inhibited by 2,3-dimercaptopropanol (BAL). Neither malonate nor succinate affects acid secretion or oxygen uptake under conditions designed to facilitate their entrance into cells. Succinoxidase activity in extracts of stomachs is only slightly if at all affected by prior stimulation of the stomach to secrete. GSH is reduced by IAAm or NEM. Addition of GSH does not reverse inhibition. GSH oxidase is absent from extracts, but the stomach reduces GSSG. Extracts contain methyl glyoxalase, but addition of crude methyl glyoxal inhibits acid secretion. CoA is reduced by NEM parallel with NEM's effect on secretion. IAAm has little effect on CoA. Addition of CoA does not reverse inhibition. Benemid inhibits acid secretion, and its effect is additive with that of NEM and 2,4-dinitrophenol. The lipoic acid content as assayed by S. faecalis is unaffected by IAAm or arsenite and only by high concentration of NEM. The effect of arsenite is strongly additive with that of the other inhibitors. Diphenylchloroarsine inhibits and is not reversed by GSH. No certain conclusions concerning the relation of metabolism and function can be drawn from this work.
Categories of Parabiotic Intoxication: Further Evidence That the Condition Results From Unequal Cross Transfusion
Authors: Hall C. E. , Hall O.
Published: December 2017

Hematologic studies of parabiotic rats indicate that in addition to pairs in which one twin exhibits anemia and the partner hyperemia (parabiosis intoxication), there are pairs in which an anemic or a hyperemic rat has a normal co-twin. The hematologic status of parabionts cannot accurately be deduced from their coloration, and hence visual categorization of pairs as normal or ‘intoxicated’ is unreliable. Death of one of the partners always causes a fatal anemia to develop in the previously normal twin in healthy pairs, and usually produces the same condition in the previously erythremic partner in intoxicated pairs. The findings are interpreted to mean that the hematologic inequalities of intoxicated pairs represents the effect of unequal transfusion, with one partner gaining blood at the expense of the other; and are thought to be inconsistent with the contention that the anemia of parabiosis intoxication is hemolytic in nature and the erythremia a sludging of erythrocytes resulting in interference with their negotiation of the capillary anastomosis.
Blood Volume, Intracellular and Extracellular Fluid Spaces in Normal Dogs and in Dogs With Ascites Secondary to Severe Tricuspid Insufficiency
Authors: Balkissoon Basdeo , Spellman Mitchell W. , Hawthorne Edward W.
Published: December 2017

Twenty-two normal and 12 dogs with ascites secondary to surgically induced isolated, total tricuspid insufficiency or a combination of tricuspid insufficiency with bilateral arteriovenous fistulae in the hind extremities were studied. In the ascitic animals: a) the blood volume, as determined by the use of rose bengal dye, increased secondary to an elevation in the plasma volume. b) The total body water, as measured by use of antipyrine, remained unchanged but the thiocyanate space increased and the calculated intracellular space was comparably diminished. c) The excretory hepatic function as evaluated by the rose bengal dye method was significantly depressed whereas the capacity of the liver to excrete bromsulfalein was not impaired. This investigation provides a basis for evaluating the influences of adrenalectomy among a similar group of ascitic dogs with tricuspid insufficiency.
Isotonic NaCl Diuresis in Rats
Authors: Jacobson H. N. , Kellogg R. H.
Published: December 2017

Prolonged, steady state, isotonic saline diuresis was produced by intravenous infusion in single, unanesthetized rats. The actions of single, intravenous doses of vasopressin, oxytocin and posterior pituitary solution were studied, with particular emphasis on concurrent changes of NaCl and water excretion. During isotonic saline diuresis vasopressin was antidiuretic, and in larger doses, chloruretic. Oxytocin was diuretic and chloruretic. Posterior pituitary solution was phasically diuretic and strongly chloruretic. Suitable doses of each were also injected during infusions of 0.6, 0.3, 0.23, 0.15, 0.077, 0.030 and 0.00 m NaCl, sufficient dextrose being added in the last three to make the infusate isotonic with blood. The effects of these infusates on the antidiuretic and chloruretic action of vasopressin, oxytocin and posterior pituitary solution are described. In general, decreasing the NaCl content of the infusion enhanced antidiuretic action and tended to conceal chloruretic action. Conversely, increasing the NaCl content of the infusion, within physiological limits, enhanced chloruresis, diminished antidiuretic action and enhanced diuretic action. Chloruresis blocked or even reversed an expected antidiuresis. The bearing of these findings on methods of assaying materials for their effects on NaCl and water excretion is discussed briefly.
Adaptations to Intraperitoneal Sucrose Solutions in the Rat
Authors: Iampietro P. F.
Published: December 2017

Rats injected intraperitoneally with sucrose solution (1.5 m) two or more times at weekly intervals adapt by increasing the concentration of sucrose in the urine at 1–3 hours and by increasing urine output at the end of 6 hours. The adaptation appears within 2 days after the first injection and disappears after 13 days of no injections. There is no adaptation in absorption from the peritoneal cavity. The adaptation in excretion may therefore be the result of reduced tubular reabsorption of sucrose. Adaptations were observed also in drinking responses and in survival when toxic doses were administered.
Removal of Excess Cholesterol and Cholate by the Isolated Rat Liver From its Perfusate
Authors: Friedman Meyer , Bine René , Ishida Tad
Published: December 2017

Perfusion of the isolated perfused rat liver with a perfusate containing hypercholesteremic and hypercholatemic blood results in the removal of some of the cholesterol and almost all of the excess cholate. The withdrawn cholesterol is deposited almost completely in the liver, whereas the withdrawn cholate is excreted promptly in the bile. It is concluded that the isolated liver behaves qualitatively similar to the liver of the intact rat in respect to cholesterol and cholate metabolism.
Role of Urea in Rat Proteinuria
Authors: Finlayson J. S. , Baumann C. A.
Published: December 2017

Dietary casein and soy protein were equally effective in increasing the normal proteinuria of the male rat. Urea fed ad libitum increased proteinuria, but the increase was usually less than that due to an isonitrogenous level of casein. Urea fed 2 hr/day brought on a rapid increase in proteinuria, which over the rest of the day followed neither the blood levels of urea nor the intake of water. An amino acid mixture, prepared to imitate the composition of casein, increased proteinuria to that caused by an isonitrogenous addition of urea but less than that caused by the equivalent high protein diet. Varying the level of vitamin B6 had no effect on the proteinuria of rats on several different diets. A simplified method for the routine estimation of rat urinary protein by centrifugation is presented.
Transtubular Water Movement in the Isolated Doubly-Perfused Bullfrog Kidney
Authors: Swanson Robert E. , Hoshiko T. , Visscher M. B.
Published: December 2017

Deuterium oxide (D2O) was perfused through either the arterial or the portal system of the isolated doubly-perfused bullfrog kidney. Admixture of the two fluids at the level of the peritubular capillaries makes it possible to regulate independently the composition of the glomerular filtrate and the peritubular fluid. The appearance of large amounts of labeled water in the urine when D2O was perfused through the portal system demonstrates a bidirectional water movement across the renal tubule. Furthermore the urine D2O concentration was, on the average, between 80–90% that of the renal vein perfusate (the latter was assumed to be similar in composition to peritubular capillary fluid). The apparent failure to reach complete equilibrium was shown to be due to an inhomogeneous flow distribution within the kidney. When the flow pattern was determined and the urine D2O content predicted on that basis, 100% equilibration of the isotope was established. These results are in agreement with the prediction, based on present concepts of proximal tubule water reabsorption, that tubule fluid should be 90% equilibrated before 1% of the proximal tubule is traversed.
Right Ventricular Contraction
Authors: Anzola Jorge
Published: December 2017

Cyclic changes in the dimensions of the right ventricular wall were recorded continuously in 17 intact, unanesthetized dogs. The free wall of the right ventricle contracts synchronously. At six different locations on its surface, the average relative shortening was about 15%. At the onset of ventricular systole, the right ventricular wall expands while the intraventricular pressure abruptly rises. This initial systolic expansion of the wall represents a change in shape of the chamber without a change in volume since the valves are all closed at this instant. It may result from early contraction of papillary muscles, drawing the tricuspid valves down into the ventricular chamber, supplemented by the bulging of the interventricular septum which accompanies sphericalization of the left ventricle at the onset of systole. During feeding, the heart rate accelerates, and the systolic and diastolic dimensions are promptly reduced. During exertion, the heart rate increased, systolic ejection was much more complete and diastolic filling was somewhat reduced.
Quantitative Aspects of Antithrombin and Heparin in Plasma
Authors: Waugh David F. , Fitzgerald Marie A.
Published: December 2017

An examination is made of the characteristics of antithrombin and heparin in plasma as described in the literature. Antithrombin action follows the equation - dT/dt = k1T(A0 – T0 + T – k2t) + k2 where T, A and t refer to thrombin, antithrombin and time in minutes, respectively. One unit of antithrombin is considered to inactivate one NIH unit of thrombin. Subscripts refer to initial concentrations. The rate constant k1, = 0.0066 ± 0.0007 refers to an apparent bimolecular reaction between thrombin and antithrombin and the rate constant k2 = 0.008 ± 0.0014 to an apparent zero order thrombin decay. A comparison of the effect observed when heparin is added to plasma with those obtained on an isolated heparin cofactor preparation ( Arch. Biochem. & Biophys. 58: 431, 1955) suggests that an independent heparin cofactor does not exist in normal plasma. The action of heparin in plasma may be accounted for quantitatively by two effects. First, an increase by a factor of approximately 20 in the rate at which antithrombin inactivates thrombin and second, a decrease in the capacity of antithrombin to inactivate thrombin by a factor of 1.9 or 2.2, depending on whether or not a small (15%) portion of the antithrombin normally present is insensitive to heparin. It is suggested that isolated ‘heparin cofactors’ originate from normal antithrombin. Saline dilution of plasma produces a profound change in antithrombin capacity as well as in rate of thrombin inactivation. The minimum capacity (35% of normal when referred to 1 ml original plasma) occurs at a 3-fold plasma dilution, about 90% of the original capacity reappearing when a 20-fold dilution is used.
Immediate Capillary Stress Response
Authors: Kramár Jenö , Meyers V. William , Simay-Kramár Margarete , Wilhelmj Charles M.
Published: December 2017

Beside the previously described changes in capillary resistance occurring after a period of latency and lasting for several days or weeks, another type of response was found in both human subjects and experimental animals which sets in promptly and wears off within 4 hours. It is suggested that this be termed ‘immediate capillary stress response’ for the sake of distinction from the ‘late capillary response.’ Both immediate and late responses may show patterns of increase, decrease and biphasic reaction or there may be upon the same stress no change in the capillary resistance at all. Since the immediate capillary stress response, in contrast to the late response, appears in the adrenalectomized animal as well as in the intact animal, it is postulated not to be dependent on the adrenal cortex.
Cardiotonic Activity of Some Adrenal Steroids
Authors: Emele Jane Frances , Bonnycastle Desmond D.
Published: December 2017

The inotropic activity of Compounds A acetate, B, E, F, S and DCA was determined upon hypodynamic papillary muscles (cat) (bathed in Krebs-Hensleit solution, ph 7–7.2, with the calcium content reduced to 1.0 mEq./l., and driven by a square wave stimulator at a rate of 1/sec., threshold voltage, duration 3 msec.). The effects obtained were contrasted with the cardiotonic activity determined in the same manner for serum, serum albumen and a dialysate of albumen. It is concluded, that while low concentrations of compound B (10–25 µg %), compound F (10–500 µg %), compounds E and S (10 µg %) did exert a positive inotropic action, and while higher concentrations of these and all concentrations of DCA and compound A were depressant to the papillary muscle, these steroids did not account for the positive inotropic activity obtained with 10% serum, 1% serum albumen or the dialysate of 1% albumen (greatest activity with this last).
A Physiologic Reference Point for Measuring Circulatory Pressures in the Dog—Particularly Venous Pressure
Authors: Guyton Arthur C. , Greganti Frank P.
Published: December 2017

A physiologic reference point for measuring pressures in the circulatory system has been located by rotating dogs into all positions in space and locating the axes of rotation at which least variation in right atrial pressure occurs. This point remains extremely precise from one animal to another and also extremely precise regardless of the state of the circulation of the animal. The apparent reason for such precise localization is that the heart operates as a feedback control system for controlling the end-diastolic pressure in the right ventricle; that is, increasing the end-diastolic pressure increases cardiac output, and this automatically returns the end-diastolic pressure back toward normal. The physiologic reference point was found to be located approximately in the lower portion of the right ventricle described by the following dimensions: a) midway between the two lateral margins of the chest; b) anterior to the back 0.614 times the thickness of the chest; c) caudal to the sternal notch 0.767 times the distance from the sternal notch to the tip of the xiphoid process.
Functional Recovery Following Vagosympathetic Anastomosis in the Cat
Authors: Guth Lloyd
Published: December 2017

Vagosympathetic anastomosis was performed in cats to direct regenerating vagal fibers to the superior cervical sympathetic ganglion. Two weeks postoperatively myosis, nictitating membrane prolapse and loss of ear temperature regulatory function were observed. By the 8th postoperative week ear temperature function had returned to normal although ocular signs of sympathetic paralysis remained. Pupillary dilatation and nictitating membrane retraction did occur at times ordinarily associated with vagal activity (accompanying feeding). Transection of the regenerated vagus nerve abolished both ocular feeding reflex and the recovered ear temperature regulatory function.
Accumulation of Ascites During Maintenance of Adrenalectomized Dogs With Thoracic Inferior Vena Cava Constriction on a High Sodium Diet Without Hormone Therapy
Authors: Davis James O. , Howell David S. , Goodkind M. Jay , Hyatt Robert E.
Published: December 2017

Adrenalectomized dogs with thoracic inferior vena cava constriction and ascites were maintained on a high Na regimen (160–240 mEq/day of Na) without replacement therapy. Maintenance was successful only after Na citrate was added to the high salt diet to prevent acidosis. When the quantity of ingested Na exceeded that excreted by the kidneys in three of the four animals, Na retention occurred and ascites accumulated. The large intake of Na required to exceed the high rate of renal Na excretion emphasizes the important role of the adrenal cortex in the pathogenesis of ascites.
Metabolism of Iodinated Casein in the Rat
Authors: Friedberg Wallace , Reineke E. P.
Published: December 2017

Radioactive (I131) iodinated casein was prepared under conditions established previously for maximum formation of thyroxine in such preparations. Iodide and loosely combined iodine were removed by dialysis against flowing tap water. Tissue distribution studies of radioactivity 100 minutes after intravenous injection of radioactive iodinated casein showed maximum concentration in the liver, followed in decreasing order by spleen, kidney, stomach, lung, small intestine and large intestine. In further experiments thyroparathyroidectomized rats were injected intravenously with iodinated casein solutions; blood and liver samples were obtained at varying intervals after injection, and the samples were fractionated into a) free and b) combined thyroxine-like compounds. Within 1 1/2 hours after injection both free and combined thyroxine-like compounds were found in both blood plasma and liver. Similar determinations at 24 and 72 hours showed the rapid disappearance of combined thyroxine-like compounds from plasma and their concentration in the liver. Simultaneously there was a pronounced increase in the ratio of free to total thyroxine-like compounds in plasma. These findings are believed to indicate that the liver is the principal site for the liberation of thyroxine from iodinated proteins when the latter are administered parenterally, and the free compounds are returned to the blood stream. The thyroidal action of iodinated proteins given by this route can then be explained as the action of the free thyroxine or related compounds that are so released.
Metabolism of Carbon 14 Methyl-Labeled Sodium Acetate Following Thermal Trauma in the Rat
Authors: Braasch John W. , Levenson Stanley M. , Crowley Leo V. , Vinecour H. Mortye , Vinecour Julia A.
Published: December 2017

Observations on the metabolism of C14 methyl-labeled sodium acetate have been obtained in 14 control and 11 burned rats. The C14 acetate was given intraperitoneally 3 days after ether anesthesia (control) or after anesthesia and thermal trauma. The losses of C14 in expired air and urine were measured in both groups. The data suggest that tissue protein synthesis from acetate is proceeding in the burned rats and at rates which are almost certainly not slower than in normal rats. This would suggest that generalized antianabolism is not the basis for the increased urinary nitrogen excretion after burns.
Effect of Sympathetic Nerve Stimulation on Cutaneous Small Vein and Small Artery Pressures, Blood Flow and Hindpaw Volume in the Dog
Authors: Kelly William D. , Visscher Maurice B.
Published: December 2017

Electrical stimulation of the lumbar sympathetic chain in dogs produced a variety of response patterns in pressures measured in the femoral artery, a small cutaneous artery (saphenous) and a small cutaneous vein. The preponderant response in the small vein during stimulation was a rise from an average control value of 17 mm Hg to an average value of 30 mm Hg. Shortly after cessation of stimulation a secondary pressure rise occurred to an average value of 42 mm Hg. The average small artery pressure changed from 99 mm Hg to 138 mm Hg during stimulation and fell to 55 mm Hg shortly after stimulation ended. Both pressures then gradually returned to control levels. Hindpaw volume and saphenous artery blood flow invariably showed an abrupt decrease during sympathetic nerve stimulation. An increase in small vein pressure associated with decreased blood flow is interpreted to be due to an increase in resistance to run off from the venous bed. Marked increases in small vein pressure occurred following sympathetic stimulation for as long as ten minutes after cessation of respiration and cardiac contraction. Control experiments excluded changes in cardiac output, central venous pressure and skeletal muscle movement as significant factors in the observed changes. Therefore the small veins as well as the small arteries of the skin of the hindpaw in the dog are capable of constricting in response to sympathetic nerve stimulation to produce marked increases in intraluminal pressure. The small vein can react independently of the small artery.
Relation of Experimental Tachycardia to Amplitude of Motor Activity and Intensity of the Motivating Stimulus
Authors: Dykman Ross A. , Gantt W. Horsley
Published: December 2017

The heart rates accompanying three auditory signals for three different intensities of electric shock are proportional to these three intensities and also parallel to the amplitudes of the motor responses (Crs) and inversely proportional to the latent period of the motor Crs. There is thus a close relationship between the intensity of the reenforcing shock and the learned responses to the signals for the shocks, whether the response be in the ‘voluntary’ motor system or in the ‘involuntary’ autonomic (cardiac) system. Since the intensity of the shock (unconditional stimulus) is analogous to ‘motivation,’ we see here that the acquired change in heart rate (tachycardia) in such an experiment where the stress is not sufficient to produce pathology and chaotic relations, and where the conditions are kept constant, is proportional to the intensity of the motivation.
Potassium and the Hypothermic Heart
Authors: Mavor G. E. , Harder R. A. , McEvoy R. K. , McCoord A. B. , Mahoney E. B.
Published: December 2017

During surface cooling to 26° with respiratory control to prevent hypercapnia, the plasma K level falls. Plasma glucose levels parallel the K variations. There is some evidence of failure of utilization of glucose at low temperatures. A marked negative coronary arteriovenous K difference develops during caval occlusion and circulatory arrest.
Renin Tachyphylaxis and ‘Renin Hypertension’ in the Rabbit
Authors: Schapiro Shawn , Gordon David B. , Drury Douglas R.
Published: December 2017

A ‘renin hypertension’ was produced by means of a constant intravenous infusion of a carefully quantitated renin solution. Renin injections were then superimposed to the point of tachyphylaxis. In all cases when tachyphylaxis was established, the blood pressure gradually returned to preinfusion levels. This occurred in spite of continuance of the renin infusion. As renin tachyphylaxis does not lower the blood pressure of renal hypertensive animals, this suggests that ‘renin hypertension’ and renal hypertension are qualitatively different entities.
Biosynthesis of Fatty Acids in Liver and Intestine of Intact Normal, Fasted and X-Irradiated Rats
Authors: Coniglio John G. , McCormick Donald B. , Hudson Granville W.
Published: December 2017

A 72-hour fasting period affects intestinal incorporation of C14-acetate into fatty acids to a smaller extent that it does hepatic incorporation. Glycogen concentration and hepatic incorporation of acetate into fatty acids increases in irradiated, fasted rats (750 r total-body x-irradiation) compared to fasted controls. Intestinal incorporation of C14-acetate into fatty acids decreases in the irradiated rat. A direct relationship between the amount of liver glycogen present and the amount of incorporation of C14 into fatty acids was not observed at these levels of hepatic glycogen and lipogenesis.
Effects of Certain Indole Amines on Electrical Activity of the Nervous System
Authors: Slocombe Alan G. , Hoagland Hudson , Tozian Lillian S.
Published: December 2017

Lysergic acid diethylamide (LSD), 5-hydroxytryptamine, and adrenochrome were shown to have properties similar to epinephrine in their effects on the spontaneous electrical activity in the brain of the albino rat. The effects of these drugs were shown to be determined by the type of anesthetic used. In Pentothal-anesthetized animals, profound reduction of the electrical activity in both frequency and amplitude was found in response to these drugs, while in ether-anesthetized animals there was no significant effect. There was a tendency for LSD to increase electrical activity when injected following recovery from anesthesia. The significance of this differential response is discussed with respect to structures in the central nervous system primarily affected by ether and Pentothal, and it is suggested that the site of action of these compounds is in Pentothal-sensitive nonspecific pathways. The site of the depressive action of these drugs with Pentothal is further defined by the fact that both cortical and subcortical structures were equally affected, while respiratory and cardio-regulatory centers were not significantly depressed. This implicates one of the lower nonspecific centers with widespread cortical and subcortical projections.
Coronary Blood Flow and Myocardial Metabolism During Hypoxia in Adrenalectomized-Sympathectomized Dogs
Authors: Hackel Donald B. , Clowes George H. A.
Published: December 2017

The coronary blood flow and carbohydrate metabolism of the heart during hypoxia were studied in two groups of dogs: a) intact animals, and b) those subjected to adrenalectomy and thoracic sympathectomy. The coronary sinus was catheterized via the external jugular vein. The coronary blood flow was measured by the nitrous oxide desaturation technique, and the coronary arteriovenous differences of oxygen, glucose, lactate and pyruvate were determined. A similar increase in coronary blood flow and a comparable change in myocardial carbohydrate metabolism were found during hypoxia in both groups of animals. In the adrenalectomized and partially sympathectomized dogs these changes took place without the increase in heart rate or blood pressure found in the intact animals. It is concluded that the increase in coronary blood flow during hypoxia is not necessarily mediated by either the cardiac sympathetic nerves or the adrenal glands. Local metabolic factors are the primary determinants of coronary blood flow.
Pressure-Circumference Relations of Left Ventricle
Authors: Rushmer Robert F.
Published: December 2017

Changes in left ventricular pressure and left ventricular circumference of intact animals have been recorded simultaneously during spontaneous and induced cardiovascular responses. Mechanisms by which the left ventricular myocardium alters its ‘work output’ are indicated by pressure-circumference loops displayed on a cathode ray oscilloscope. Evidence is presented that the external work of the heart is not necessarily related to the diastolic dimensions in accordance with Starling's law of the heart. Instead, changes in both myocardial contractility and distensibility may play important roles in cardiac adaptation to various conditions.