bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac function and metabolism during cholinergic stimulation in the newborn lamb
Authors: Downing S. E. , Lee J. C. , Taylor J. F.
Published: December 2017

This study was designed to assess the influences of cholinergic stimulation on coronary flow (CF), oxygen metabolism (MVO2) and contractility (MC) of the left ventricle in the newborn. Nineteen lambs, 1-7 days of age, were anesthetized with pentobarbital (20 mg/kg) and prepared for continuous measurement of CF, heart rate (HR), aortic (AP) and left ventricular end-diastolic (LVEDP) pressures, dP/dt max, and cardiac output (CO). HR, AP, and CO could be controlled as desired. Simultaneous arterial and sinus blood samples were analyzed for O2 content, hematocrit, pH, PO2, and PCO2. LV MVO2 and %O2 extraction (Ext) were calculated. Acetylcholine (ACh) infusion (30-50 microgram/min-kg) caused an increase of LVEDP (4 cmH2O), but no significant change in dP/dt max or HR with constant AP and CO. CF increased by 44%, but MVO2 per beat was unchanged. Similar changes were observed with constant HR (pace). Suramaximal efferent stimulation of right or left vagus nerves produced bradycardia (77-68 beats/min) but no significant changes in contractility, CF, Ext, or MVO2. These findings were unaltered by beta blockade. The changes elicited by ACh infusion or vagal stimulation were abolished by giving atropine. It is concluded that although cholinergic sensitivity can be demonstrated, vagal stimulation does not importantly influence MC, CF, or MVO2 in the lamb. This may relate to incomplete development of the adrenergic system.
Barrier and uptake mechanisms in the cerebrovascular response to noradrenaline
Authors: McCalden T. A. , Eidelman B. H. , Mendelow A. D.
Published: December 2017

Cerebral blood flow (CBF) was measured in 20 baboons by the intra-arterial xenon-133 injection method. The CBF responses to intra-arterial infusions of noradrenaline (NA) were determined. These responses were normally found to be vasodilator and mediated by beta adrenoreceptors. After infusion of substances blocking extraneuronal uptake of NA or opening of the blood-brain barrier, this vasodilation was either abolished or converted to an alpha-receptor mediated vasoconstriction. This suggests that normally the cerebral circulation is protected against noradrenergic vasoconstriction by mechanisms reducing the concentration of NA in the tunica media to below threshold for alpha-adrenoreceptor stimulation.
Systemic hemodynamic effects of microspheres in conscious rats
Authors: Tsuchiya M. , Walsh G. M. , Frohlich E. D.
Published: December 2017

The effect of increasing quantities of carbonized microspheres (15 +/- 5 micrometer diam) on systemic hemodynamics was evaluated in 21 Sprague-Dawley, 6 normotensive Wistar-Kyoto (WKY), and 8 spontaneously hypertensive (SHR) male rats. Total cumulative injections of more than 100,000 microspheres produced significant systemic hemodynamic alterations manifested by decreased oxygen consumption, cardiac output, and mean arterial pressure; and by increased heart rate, total peripheral resistance, and arterial-venous blood oxygen content difference. There were no hemodynamic alterations characteristic of any rat species, and reproducibility of three separate injections of 20,000 microspheres in each rat was excellent.
Effects of decreasing lung compliance with oleic acid on the cardiovascular response to PEEP
Authors: Scharf S. M. , Ingram R. H.
Published: December 2017

In 12 anesthetized mongrel dogs on a constant volume ventilator, the response of the cardiovascular system to increasing positive end-expiratory pressure (PEEP) was examined before and after inducing acute lung injury with oleic acid. As PEEP was raised to approximately 16 mmHg, lung volume increased by approximately 900 ml before oleic acid and only 350 ml after. Pleural pressure increased by the same amount, indicating that both lung and chest wall compliance decreased with oleic acid. Right atrial pressure, the back pressure to venous return, also increased by the same amount. Although cardiac output at PEEP = 0 was lower after oleic acid, the relative decrements produced by increasing PEEP were the same as before oleic acid.
Measurement of local cerebral blood flow with iodo [14C] antipyrine
Authors: Sakurada O. , Kennedy C. , Jehle J. , Brown J. D. , Carbin G. L. , Sokoloff L.
Published: December 2017

The autoradiographic diffusible tracer technique for the measurement of local cerebral blood flow was originally designed for use with the radioactive, inert gas 131I-labeled trifluoroiodomethane and is applicable only with tracers that exhibit unrestricted diffusion through the blood-brain barrier. Because of the technical problems associated with the use of gaseous tracers, a suitable nonvolatile tracer has been sought. [14C] Antipyrine has been used previously and found to be unsuitable because of limitations in its diffusion through the blood-brain barrier. An analogue of [14C]antipyrine, iodo [14C]antipyrine, exhibits higher partition coefficients than [14C]antipyrine between nonpolar solvents and water and might, therefore, be expected to diffuse more freely through the barrier. Its use as the tracer in the local blood flow technique leads to values considerably above those obtained with [14C]antipyrine in the rat and cat and essentially the same as those obtained with the gas trifluoro[131I]iodomethane in the cat. Iodo[14C]antipyrine appears, therefore, to be a satisfactory nonvolatile tracer for the measurement of local cerebral blood flow.
Vascular capacitance of dog intestine using mean transit time of indicator
Authors: Rothe C. F. , Johns B. L. , Bennett T. D.
Published: December 2017

Changes in vascular volume of dog jejunum caused by norepinephrine, isoproterenol, or acetylcholine at constant=flow perfusion, were compared to changes in volume caused by changes in blood flow or venous pressure. Vascular volume was measured by indicator dilution mean transit time, using a step input of indocyanine green (125 microgram/min). Venous pressure was held at 10 mmHg; control arterial pressure was about 110 mmHg. At a control flow of 521 ml/min.kg of tissue, the vascular volume was 104 +/- 14 (SD) ml/kg of tissue. Reducing flow by 75 percent caused the volume to decrease by 29 percent (--31 ml/kg); maximal norepinephrine infusion at constant flow and venous pressure decreased the vascular volume by 24 percent, and a 10-mmHg reduction in venous outflow pressure caused a 25 percent (--27 ml/kg) reduction. On the other hand, isoproterenol (100 microgram/liter) at constant flow caused a 245 percent increase in conductance and only a 12 percent increase in vascular volume. Thus, active venoconstriction, changes in venous pressure, or changes in flow independently may cause changes in vascular volume of the intestine. Active smooth muscle changes in the venous capacitance vessels are not necessarily correlated with changes in the arterial resistance vessels.
Time course of the cerebral circulatory response to metabolic depression
Authors: Keaney N. P. , McDowall D. G. , Pickerodt V. W. , Turner J. M. , Lane J. R. , Okuda Y. , Deshmukh V. D. , Coroneos N. J.
Published: December 2017

Baboons anesthetized with halothane and N2O/O2 were given an intravenous steroid anesthetic (Althesin; Glaxo Laboratories Ltd., U.K.). The drug bolus was labeled with 99mTc, and the time from central venous injection to peak radioactivity in the brain was designated drug brain arrival (DBA-peak). The electroencephalogram slowed 1.2 +/- 0.9 s after DBA-peak (P greater than 0.2), and approximately 2 s after DBA-peak, internal carotid blood flow (ICarBF) decreased and calculated internal carotid vascular resistance (ICarVR) rose. During this 2-s delay in the cerebrovascular response to the arrival of a cerebral metabolic depressant in the brain, the decrease in mean cortical Pco2 was calculated to be less than 0.26 mmHg from cortical CO2 solubility, and less than 0.32 mmHg from cortical CO2 diffusivity, which indicated that mean cortical Pco2 changes do not control cerebral blood flow (CBF). The unaltered time course of the changes in EEG, ICarBF, and ICarVR after acute cervical sympathectomy and alpha-adrenergic receptor blockade excluded the involvement of the sympathetic nervous system in the vasoconstrictor response. Intracarotid Althesin showed that the cerebral vasoconstriction was not a direct effect of the drug. The postulated link between the effects of Althesin on CBF and cerebral metabolism remains to be elucidated but is probably indirect, involving the brainstem.
Cerebral blood flow in birds: effect of hypoxia
Authors: Grubb B. , Colacino J. M. , Schmidt-Nielsen K.
Published: December 2017

The effect of hypoxia on cerebral blood flow in ducks was investigated by the rate at which arterially injected xenon-133 was cleared from the duck's brain. A two-component clearance curve resulted, which we have attributed to flow through the grey and white matter. Decreasing the arterial oxygen tension (PaO2) to 75 mmHg had no effect on cerebral blood flow. However, decreasing the PaO2 below 75 mmHg significantly increased blood flow to the fast-clearing compartment. The greatest increase in blood flow was seen when the arterial PO2 was below 50 mmHg. At an arterial PO2 of 30 mmHg, the cerebral blood flow to the fast-clearing compartment was increased more than 600% above the normoxic level. The magnitude of this increase is much greater in the duck than has been reported for mammals at roughly equivalent arterial oxygen tensions. The ability of avian cerebral blood flow to increase at moderate levels of hypoxia, plus the magnitude of the increase, may play a role in the exceptional tolerance of birds to hypoxia.
Effect of tris(hydroxymethyl)aminomethane on ischemic myocardium
Authors: Effron M. B. , Guarnieri T. , Frederiksen J. W. , Greene H. L. , Weisfeldt M. L.
Published: December 2017

Intracellular acidosis may depress myocardial function and metabolism during ischemia. In the present study, the function and metabolism of a globally ischemic, isovolumic cat left ventricle preparation, perfused with oxygenated Krebs-Ringer biocarbonate solution, was examined. Addition of tris(hydroxymethyl)-aminomethane (Tris) (15 mM) to the perfusate at physiologic pH and PCO2 increased performance during ischemia to a greater extent and for a longer period than low PCO2 )15 mmHg), alkalotic (pH, 7.8) perfusate and a control sucrose perfusate. Under nonischemic conditions the inotropic effect of Tris was only briefly greater than sucrose perfusate. The inotropic effect of Tris during ischemia did not appear to depend on changes in coronary flow, oxygen consumption, sodium concentration, perfusate osmolality, or catecholamine release. During ischemia, lactate production was unchanged with Tris, but increased with low PCO2-alkalosis. Tissue levels of ATP and creatine phosphate for control ischemic hearts did not differ from Tris-perfused or low PCO2-alkalosis hearts. Thus, Tris appears to exert an inotropic effect that is more prominent in ischemic than nonischemic myocardium. The results are consistent with the possibility that Tris acts as an intracellular buffer to increase the efficiency of energy production and/or utilization during ischemia.
Bone blood flow measured by 85 Sr microspheres and bone seeker clearances in the rat
Authors: Schoutens A. , Bergmann P. , Verhas M.
Published: December 2017

This paper investigates further the relationship between the initial bone clearance of a bone-seeking radioisotope or labeled substance and the bone blood flow. The bone blood flow of rats was modified over the widest possible range of physiological values by heating and cooling their hindlimbs. Osseous blood flow was measured by the arteriolar trapping of labeled microspheres of 15 micrometer diameter injected into the left ventricle. The plasma clearances of 45Ca and 99 m Tc by bone were measured 10 min after the intravenous injection of radiocalcium and of 99 m technetium pyrophosphate. The extraction ratio for 45Ca over the 10-min interval (45Ca clearance/bone plasma flow) was 0.60 for low blood flows, 0.40 for blood flows at rest, and 0.25 for high values of flow. The data for 99 m Tc were, respectively, 0.68, 0.34, and 0.22. Initial bone clearances of either substance should not be used to measure the increases in bone blood flow over the values at rest.
Modulation of adrenergic transmission by angiotensins in the perfused rat mesentery
Authors: Campbell W. B. , Jackson E. K.
Published: December 2017

Isolated rat mesenteric arteries perfused with a modified Krebs solution were utilized to study the effects of angiotensin II (AII), angiotensin III (AIII), and [des-Asp1-Arg2]AII on adrenergic transmission. Angiotensin II potentiated vasoconstrictor responses to both sympathetic nerve stimulation and to exogenous norepinephrine, whereas AIII and [des-Asp1-Arg2]AII potentiated vasoconstrictor responses to exogenous norepinephrine only. When the responses to exogenous norepinephrine were compared, the order of agonist potency was AIII greater than AII greater than [des-Asp1-Arg2]AII. The potentiation of sympathetic nerve stimulation by AII was inhibited by simultaneous administration of AIII (25%), [des-Asp1-Arg2]AII (51%), [Sar1-Ile8]AII (83%), and (Ile7)AIII (80%). The potentiation of exogenous norepinephrine by AII, AIII, and [des-Asp1-Arg2]AII was inhibited by [Sar1-Ile8]AII (110%, 113%, and 108%, respectively) and by [Ile7]AIII (50%, 64%, 91%, respectively). We conclude that AII possesses the capacity both to increase norpinephrine release during sympathetic nerve stimulation and to decrease norepinephrine reuptake, whereas AIII and [des-Asp1-Arg2]AII decrease norepinephrine release and reuptake. Also, under conditions of increased N-terminal degradation of AII, blockade of norepinephrine reuptake would be increased while the release of norepinephrine by nerve stimulation would be reduced.
Regional diastolic mechanics of the left ventricle in the conscious dog
Authors: Ling D. , Rankin J. S. , Edwards C. H. , McHale P. A. , Anderson R. W.
Published: December 2017

In eight chronically instrumented conscious dogs, apical and middle left ventricular transverse diameters were measured with pulse-transit ultrasonic dimension transducers. Intracavitary apical and midventricular pressures and intrapleural pressure were measured with micromanometers. Both diameters were normalized as a percent extension from the dimension at zero transmural pressure, determined during a transient vena caval occlusion. During the rapid phase of diastolic filling, there was a 2--5 mmHg pressure gradient from the midventricle to the apex. During late rapid filling, the apical transmural pressure and diameter increased more rapidly and reached diastasis 17 +/- 4 ms earlier than the corresponding midventricular measurements (P less than 0.01). The static diastolic pressure-dimension characteristics at the apical and midventricular levels were not significantly different (P greater than 0.30). The dynamic diastolic pressure-dimension relationship was also similar at the two levels and could be represented by a model incorporating parallel viscous properties. Because of regional differences in pressures and dimensions, however, the dynamic relationship could not be modeled when pressure was compared to the dimension at a different level. Thus, diastolic pressures should be measured at the same level as dimensions when assessing left ventricular diastolic mechanics.
Renin-angiotensin system in stroke-prone spontaneously hypertensive rats
Authors: Shibota M. , Nagaoka A. , Shino A. , Fujita T.
Published: December 2017

The development of malignant hypertension was studied in stroke-prone spontaneously hypertensive rats (SHR) kept on 1% NaCl as drinking water. Along with salt-loading, blood pressure gradually increased and reached a severe hypertensive level (greater than 230 mmHg), which was followed by increases in urinary protein (greater than 100 (mg/250 g body wt)/day) and plasma renin concentration (PRC, from 18.9 +/- 0.1 to 51.2 +/- 19.4 (ng/ml)/h, mean +/- SD). At this stage, renal small arteries and arterioles showed severe sclerosis and fibrinoid necrosis. Stroke was observed within a week after the onset of these renal abnormalities. The dose of exogenous angiotensin II (AII) producing 30 mmHg rise in blood pressure increased with the elevation of PRC, from 22 +/- 12 to 75 +/- 36 ng/kg, which was comparable to that in rats on water. The fall of blood pressure due to an AII inhibitor, [1-sarcosine, 8-alanine]AII (10(microgram/kg)/min for 40 min) became more prominent with the increase in PRC in salt-loaded rats, but was not detected in rats on water. These findings suggest that the activation of renin-angiotensin system participates in malignant hypertension of salt-loaded stroke-prone SHR rats that show stroke signs, proteinuria, hyperreninemia, and renovascular changes.
Effects of acidosis on mechanical function and Ca2+ exchange in rabbit myocardium
Authors: Poole-Wilson P. A. , Langer G. A.
Published: December 2017

The effects of acidosis on myocardial function and calcium exchange have been studied in the isolated but arterially perfused interventricular septum of the rabbit. Temperature was 28 degrees C and stimulation rate 48 beats/min. Acidosis was induced either by increase of the perfusate PCO2 (pH reduced from 7.35 to 6.68) or by decrease of the bicarbonate-chloride ratio (pH 7.35 to 6.72). The effect on calcium efflux was assessed by introduction of acidosis at different times during the washout of 45Ca2+ from the muscle. The uptake of 47Ca2+ was recorded directly with a NaI crystal and counter. An increase of perfusate PCO2 caused a rapid fall in developed tension. The efflux of slowly exchanging 45Ca2+ and the uptake of 47Ca2+ were inhibited. There was no rapid displacement of calcium from the muscle. Decrease of the bicarbonate-chloride ratio caused a slower fall of developed tension and neither the efflux nor uptake of calcium were altered. These results suggest that developed tension and calcium exchange in the myocardium are more responsive to acidosis within the cell or cell membrane than to extracellular acidosis.
Variability in erythrocyte deformability among various mammals
Authors: Smith J. E. , Mohandas N. , Shohet S. B.
Published: December 2017

Deformability is an important aspect of erythrocyte physiology and has been extensively studied using human red cells. We have studied erythrocytes from 25 different animals using a viscometric technique. Erythrocyte diameters ranged from 3.3 microns in the goat to 11.4 microns for the elephant seal. Erythrocytes from most species deformed readily when a fluid shear stress was applied. A deformability index of the stressed cell defined as (length - width)/(length + width) correlated with cell size. The erythrocytes of four animals (pygmy goat, goat, Batanga horse, and miniature horse) deformed less than most species. Camel and llama erythrocytes, which were ellipsoidal, did not deform but oriented in the stress field.
Pyridoxal phosphate inhibition of platelet function
Authors: Kornecki E. , Feinberg H.
Published: December 2017

The effect of pyridoxal phosphate (PLP) on human platelet function in vitro was studied. PLP inhibited adenosine diphosphate (ADP)-induced shape change, aggregation, and the potentiation by ADP of arachidonic acid-induced aggregation. This inhibition could easily be reversed by increasing concentrations of ADP or by removing PLP. The addition of sodium borohydride to PLP-treated platelets produced an irreversible inhibition of ADP aggregation. Thus it is possible that PLP inhibited ADP-induced platelet function by forming a Schiff base with platelet-surface amino groups. PLP also produced a partial inhibition of platelet aggregation to epinephrine, arachidonic acid, A23187, and a dose-dependent inhibition of [14C]serotonin release to epinephrine and arachidonic acid. PLP did not inhibit [14C]serotonin release to A23187, nor did it suppress arachidonic acid-induced malondialdehyde production. The conclusion is drawn that the partial inhibition by PLP of platelet aggregation observed to epinephrine, arachidonic acid, and A23187 resulted from PLP's inhibition of the effect of released ADP.
Pulmonary interstitial compliance and microvascular filtration coefficient
Authors: Goldberg H. S.
Published: December 2017

Static and dynamic properties governing the fluid movement into the pulmonary interstitium were examined in isolated canine lobes. The system was driven by altering intravascular presure (Piv) when the lobe was isogravimetric (change in weight (W) = 0) and allowing the lobe to become isogravimetric again. By making use of an analogy to charging a capacitor across a resistor, calculation of the filtration coefficient for transvascular fluid movement (KF) and determination of the pressure-volume relationship of the pulmonary interstitial space (Pis-Vis), with a minimum of untested assumptions, was possible. KF was found to be the same for fluid moving out of or into the intravascular space, and when the relationship between Piv and alveolar pressure (PAlv) was constant, KF was independent of transpulmonary pressure (PL). When PAlv exceeded Piv, changes in Piv did not influence KF, suggesting no significant change in either surface area available for fluid transudation or vascular permeability. The Pis-Vis curve for increasing values of Vis and Pis is best described by an exponential relationhip and is independent of PL. However, the Pis-Vis curve with decreasing values of Vis and Pis is dependent on PL.
Antipyrine and aminopyrine permeability of individually perfused frog capillaries
Authors: Curry F. E.
Published: December 2017

The mechanisms of transport of water and solutes across both hydrophilic and lipophilic pathways in the capillary wall were investigated. Paired measurements of the osmotic reflection and solute permeability coefficients of a lipid soluble solute (antipyrine MW 188 or aminopyrine 231) and a hydrophilic solute (glucose 180) were made on individually perfused capillaries of frog mesentery at temperatures between 5 and 25 degrees C. Below 15 degrees C, the lipophilic pathway accounts for less than 10% of the flux of antipyrine across the capillary wall, whereas at 25 degrees C the lipophilic pathway accounts of 50% of the flux. These results conform to the hypothesis that water and both hydrophilic and lipophilic solutes share an extracellular pathway, but water and lipids cross the cell by entirely separate routes. Both the activation energy for antipyrine and aminopyrine diffusion in the lipophilic pathway (25.9 kcal/mol) and the estimated cell membrane-water partition coefficients of the solutes are similar to values found for mammalian erythrocytes. Lateral diffusion in the cell membranes would account for the lipophilic pathway permeability just as well as diffusion across the cell membranes.
Positive inotropic effect of acetylcholine in canine cardiac Purkinje fibers
Authors: Gilmour R. F. , Zipes D. P.
Published: December 2017

The purpose of this study was to investigate possible mechanisms to explain the positive inotropic effects of acetylcholine in canine cardiac Purkinje fibers. Action potentials and tension were recorded from Purkinje fibers in vitro using microelectrodes and a force transducer. Acetylcholine (10(-9) to 10(-4) M) produced a dose-dependent increase in tension that was blocked by atropine but not by propranolol, phentolamine, hexamethonium, or verapamil. At 10(-5) and 10(-4) M, acetylcholine increased action potential duration at 50% of repolarization (APD50) but did not affect resting membrane potential, action potential amplitude, Vmax, or action potential duration at 90% of repolarization (APD90). Isoproterenol (10(-7) M) shortened APD50 and APD90 and increased developed tension. Subsequent addition of acetylcholine (10(-5) M) prolonged APD50 and APD90 and decreased tension. Increasing extracellular Ca2+ concentration [( Ca2+]o) from 2.0 to 3.0 mM increased tension and shortened APD50. Addition of acetylcholine (10(-5) M) increased tension further and prolonged APD50. In K+-depolarized fibers high concentrations of acetylcholine (10(-4) M) restored excitability, but lower concentrations (10(-6) M) suppressed slow responses induced by isoproterenol. Thus acetylcholine alone or with elevated [Ca2+]o increased APD50 and tension and facilitated the induction of slow responses, yet in the presence of isoproterenol acetylcholine increased APD50, decreased tension, and suppressed slow responses. These effects were mediated by muscarinic receptors and were independent of catecholamine release.
Total vascular pressure-volume relationship in conscious rats with chronic heart failure
Authors: Gay R. , Wool S. , Paquin M. , Goldman S.
Published: December 2017

To define the changes in the venous circulation in chronic left ventricular (LV) failure, we measured the mean circulatory filling pressure (MCFP), blood volume, and effective vascular compliance in conscious rats with heart failure, 3 wk after coronary ligation. Rats with myocardial infarction and LV end-diastolic pressure (EDP) greater than 15 mmHg were considered to have chronic heart failure. Rats with chronic heart failure (n = 11) showed an increase (P less than 0.001) in LV EDP to 24 +/- 2 mmHg compared with 6 +/- 1 mmHg in sham-operated (n = 9) and 7 +/- 1 mmHg in normal (n = 6) rats. In the rats with chronic heart failure the MCFP was increased to 9.9 +/- 0.2 mmHg (P less than 0.001) compared with 7.6 +/- 0.2 mmHg in the sham-operated and 7.7 +/- 0.2 mmHg in the normal rats. Effective vascular compliance was determined from MCFP-blood volume curves. In rats with chronic heart failure, the effective vascular compliance was decreased to 2.40 +/- 0.08 ml X mmHg-1 X kg-1 from 3.34 +/- 0.16 in sham-operated rats and 3.35 +/- 0.22 ml X mmHg-1 X kg-1 in normal rats. The blood volume and the unstressed vascular volume of the rats with chronic heart failure were not statistically different from the sham-operated rats. These results suggest that venous capacitance is decreased in chronic heart failure, due to a decrease in effective vascular compliance with no significant change in unstressed vascular volume. Hexamethonium chloride did not alter the effective vascular compliance of the rats with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Selective vagal innervation of sinoatrial and atrioventricular nodes in canine heart
Authors: Ardell J. L. , Randall W. C.
Published: December 2017

Parasympathetic pathways mediating chronotropic and dromotropic responses to cervical vagal stimulation were determined from sequential, restricted, intrapericardial dissection around major cardiac vessels. Although right cervical vagal input evoked significantly greater bradycardia, supramaximal electrical stimulation of either vagus produced similar ventricular rates, both with and without simultaneous atrial pacing. Dissection of the triangular fat pad at the junction of the inferior vena cava-inferior left atrium (IVC-ILA) invariably eliminated all vagal input to the atrioventricular (AV) nodal region. Yet IVC-ILA dissection had minimal influence on evoked-chronotropic responses to either cervical vagal or stellate ganglia stimulation. Respective intrapericardial projection pathways, from either right or left vagi, are sufficiently distinct to allow unilateral parasympathetic denervation of the sinoatrial (SA) and atrioventricular (AV) nodal regions. Left vagal projections to the SA and AV nodal regions course primarily along and between the right pulmonary artery and left superior pulmonary vein. Right vagal projections to the SA and AV nodal regions are somewhat more diffuse but concentrate around the right pulmonary vein complex and adjacent segments of the right pulmonary artery. We conclude there are parallel, yet functionally distinct, inputs from right and left vagi to the SA and AV nodal regions.
Changes in cardiac and hypothalamic noradrenergic activity with taurine in DOCA-salt rats
Authors: Fujita T. , Sato Y. , Ando K.
Published: December 2017

We studied the role of the cardiac and hypothalamic noradrenergic systems in the hypotensive actions of dietary taurine supplementation in deoxycorticosterone acetate (DOCA)-salt rats. The supplementation with 1% taurine could reduce blood pressure when it was given after DOCA-salt hypertension had been established. The taurine supplementation could attenuate the increased depressor response to hexamethonium-induced ganglion blockade in the DOCA-salt rats. Moreover, noradrenergic activity was determined from the rate of decline of tissue norepinephrine (NE) concentration after the administration of alpha-methyl-p-tyrosine. At 23 degrees C, cardiac NE turnover was markedly accelerated in DOCA-salt rats compared with the vehicle-injected control rats, but the 1% taurine supplement restored it toward normal. In contrast, turnover time in the hypothalamus was delayed in the DOCA-salt rats compared with the control rats, whereas 1% taurine supplement normalized the hypothalamic NE turnover. Stimulation of sympathetic discharge by cold exposure (4 degrees C, 6 h) after the administration of alpha-methyl-p-tyrosine produced marked depletion of NE in most tissues. The NE deficit in both the hypothalamus and heart was significantly greater in the DOCA-salt rats than in the control rats, but the 1% taurine supplement could normalize this. Thus taurine loading could not only diminish the sympathetic overactivity under the normal condition but also attenuate the augmented hypothalamic and cardiac noradrenergic activity by cold stress in the DOCA-salt hypertensive rats. Evidence presented suggests, therefore, that the hypothalamic noradrenergic system might be involved in the hypotensive action of taurine in DOCA-salt rats.
Activation of vagal depressor reflexes by atriopeptins inhibits renal sympathetic nerve activity
Authors: Thoren P. , Mark A. L. , Morgan D. A. , O'Neill T. P. , Needleman P. , Brody M. J.
Published: December 2017

Atrial natriuretic factor decreases arterial pressure but the hypotensive response is not accompanied by the expected reflex tachycardia. The absence of reflex tachycardia might reflect a stimulating effect of atrial natriuretic factor [atriopeptins (AP)] on cardiac-sensory receptors with vagal afferents. To test the hypothesis that AP inhibit sympathetic nerve activity by activating vagal afferents we measured changes in renal sympathetic nerve activity (SNA), heart rate, and arterial pressure during injection of APII and APIII in anesthetized Sprague-Dawley rats in the intact state, after sinoaortic denervation, and after sinoaortic denervation plus bilateral vagotomy. In intact, anesthetized rats APIII (50 micrograms/kg) lowered mean arterial pressure [-31 +/- 8 (SE) mmHg] without the expected reflex increase in renal SNA and heart rate. In contrast, infusion of sodium nitroprusside in a dose that produced a similar decrease in mean arterial pressure (-29 +/- 9 mmHg) evoked a significant increase in renal SNA (+38 +/- 8%) and heart rate (+17 +/- 5 beats/min). In rats with sinoaortic denervation, APIII induced a greater fall in mean arterial pressure (-44 +/- 8 mmHg). This hypotensive response was associated with a decrease in renal SNA (-26 +/- 2%) that was abolished by bilateral vagotomy. Atropine did not attenuate the decrease in renal SNA with APIII. We conclude that APII and APIII increase the activity of vagal afferents and thereby inhibit the increases in renal SNA and heart rate, which would be expected to result from the fall in arterial pressure. We speculate that this action might facilitate reflexly the renal vasodilator and natriuretic actions of APs.
Myogenic tone in mesenteric arteries from spontaneously hypertensive rats
Authors: Izzard A. S. , Bund S. J. , Heagerty A. M.
Published: December 2017

To investigate myogenic tone during the developmental and established phases of hypertension, segments of distal (6th order) mesenteric arteries from spontaneously hypertensive rats (SHR) at 5 and 20 wk were isolated and pressurized in vitro and compared with vessels from age-matched Wistar-Kyoto (WKY) control animals. At 5 wk, tone was significantly enhanced in the SHR. At 20 wk tone was no longer significantly increased over a wide pressure range, although arteries from the SHR were able to maintain diameter at all pressures studied, whereas vessels from the WKY exhibited forced distension at 180 and 200 mmHg. From the relative slope of the pressure-diameter relationship (myogenic index), no increase in peak myogenic responsiveness was observed in arteries from the SHR at either time point. Passive lumen diameters were significantly decreased in arteries from SHR at both time points. From the total and passive midwall circumference-tension relationships, total tension was observed at a reduced midwall circumference in the SHR, but increased absolute levels of total tension were not observed. The normalized midwall circumference-tension relationships in the two strains revealed increased total tension due to active tension development at a reduced normalized circumference at 5 wk in the SHR. At 20 wk the normalized midwall circumference-tension relationships in the two strains were identical. These results demonstrate that myogenic tone in mesenteric arteries is enhanced during the development of hypertension but not when it is established, except at high intraluminal pressures.
In vivo E-selectin upregulation correlates early with infiltration of PMN, later with PBL entry: MAbs block both
Authors: Binns R. M. , Licence S. T. , Harrison A. A. , Keelan E. T. , Robinson M. K. , Haskard D. O.
Published: December 2017

The endothelial molecule E-selectin binds most leukocyte subsets in vitro. Yet its role in regulating the very different kinetics of inflammatory infiltration of different leukocyte subsets in vivo is unclear. The kinetics of E-selectin upregulation and polymorphonuclear leukocyte (PMN) and blood lymphocyte (PBL) localization in inflammation induced by interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), phytohemagglutinin (PHA), and phorbol myristate acetate (PMA) were investigated in a well-established inbred pig trafficking model. They differed markedly both for these three labeled indicators of inflammation and in each of the four inflammatory processes. In each, E-selectin upregulation correlated with early PMN entry and later with PBL infiltration but was more protracted than both. The importance of E-selectin was confirmed by marked inhibition of PMN and PBL entry (up to > 60%) by F(ab')2 anti-E-selectin. Involvement of other molecules was illustrated by similar or greater inhibition with anti-CD18 F(ab')2. We conclude that, like CD18, E-selectin is necessary for most PMN and PBL infiltration but alone is insufficient, consistent with the involvement of several alternative multistep molecular mechanisms in this entry.
Adenosine A1 and A2 receptors mediate tone-dependent responses in feline pulmonary vascular bed
Authors: Cheng D. Y. , DeWitt B. J. , Suzuki F. , Neely C. F. , Kadowitz P. J.
Published: December 2017

Adenosine produces tone-dependent pulmonary vascular responses; however, the adenosine receptor subtype mediating these responses is unknown. In the present study, the adenosine receptor subtypes mediating tone-dependent responses were investigated, Intralobar injections of adenosine,ATP, and analogues under low-tone conditions caused dose-related increases in lobar arterial pressure; the order of potency was alpha,beta-methylene ATP (alpha,beta-metATP) > N6-cyclopentyladenosine (CPA) > ATP > adenosine. Under low-tone conditions, pressor responses to adenosine, ATP, and CPA, an adenosine A1-receptor agonist, were reduced by KW-3902, an adenosine A1-receptor antagonist, whereas KW-3902 and meclofenamate had no effect on responses to alpha,beta-metATP, norepinephrine, serotonin, or angiotensin II. Under elevated-tone conditions, injections of adenosine, ATP, and analogues caused dose-related decreases in lobar arterial pressure, and adenosine was 10-fold less potent than 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), an A2-receptor agonist, and ATP. KF-17837, an A2-receptor antagonist, reduced vasodilator responses to adenosine and CPCA, whereas responses to ATP, isoproterenol, diethylamine-NO, lemakalim, and bradykinin were not changed. The vasodilator responses to adenosine were not attenuated by Nw-nitro-L-arginine benzyl ester, methylene blue, or U-37883A. These results suggest that vasoconstrictor responses to adenosine are mediated by A1 receptors and the release of vasoconstrictor prostanoids, and that, under elevated-tone conditions, vasodilator responses are mediated by A2 receptors but not the release of nitric oxide or the activation of guanylate cyclase or K+ATP channels.
Control of skin blood flow by whole body and local skin cooling in exercising humans
Authors: Pergola P. E. , Johnson J. M. , Kellogg D. L. , Kosiba W. A.
Published: December 2017

We examined the independent roles of whole body skin temperature (Tsk) and tissue temperature (local temperature, Tloc) in the control of skin blood flow (SBF) during cooling and the roles of the vasoconstrictor (VC) and active vasodilator (AVD) systems in mediating these effects. SBF was monitored by laser-Doppler flowmetry (LDF) at untreated sites and sites with local VC blockade by pretreatment with bretylium (BT). Seven subjects underwent four sessions of moderate bicycle exercise (20-30 min duration) at neutral Tsk and Tloc (34 degrees C), neutral Tsk and cool Tloc (27 degrees C), low Tsk (28 degrees C) and neutral Tloc, and low Tsk and Tloc. Cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was expressed relative to the maximum. Cool Tsk increased the threshold level of internal temperature at which CVC began to rise equally at BT-treated and untreated sites (P < 0.05). The rate of increase in CVC relative to internal temperature was reduced by local cooling. BT pretreatment partially reversed this effect (P < 0.05). Thus a cool environment results in reflex inhibition of the onset of AVD activity by cool Tsk and a reduced rate of increase in CVC due, in part, to norepinephrine release stimulated by cool Tloc.
Developmental changes in ATP utilization during graded hypoxia and reoxygenation in the heart in vivo
Authors: Portman M. A. , Standaert T. A. , Ning X. H.
Published: December 2017

Myocardial ATP utilization and resynthesis during hypoxia and reoxygenation were studied in vivo as a function of maturation. Graded hypoxia was performed in newborn (NB; 4-10 days old, n = 6) and mature sheep (MAT; 30-60 days old, n = 6). Time-resolved 31P-nuclear magnetic resonance was used to monitor myocardial phosphates throughout hypoxia and to monitor reoxygenation concomitant with rate of myocardial O2 consumption (MVO2) measurement. Oxygen delivery and MVO2 were constant in both groups throughout hypoxia, with substantial and similar increases in both parameters during reoxygenation. Hypoxic myocardial lactate release was similar in NB and MAT. Phosphocreatine (PCr), but not ATP, decreased in NB only during milder hypoxia. Rapid PCr and slower ATP depletion occurred with severe hypoxia, consistent with ATP utilization/synthesis imbalance. Depletion rates were higher in MAT. Creatine rephosphorylation rates, measures of mitochondrial function reported as percentage of predicted values, were similar. 34 +/- 12 in NB and 26 +/- 9% in mature lambs. In conclusion, 1) phosphorylation potential decreases in NB but not MAT in response to a decreasing oxygen gradient; 2) ATP utilization during hypoxia increases more in mature lambs; 3) anaerobic ATP production is not greater in NB; and 4) despite the greater energy imbalance imposed on MAT during hypoxia, mitochondrial function is similar to NB during reoxygenation.
Cardioprotection due to preconditioning correlates with increased ecto-5'-nucleotidase activity
Authors: Minamino T. , Kitakaze M. , Morioka T. , Node K. , Komamura K. , Takeda H. , Inoue M. , Hori M. , Kamada T.
Published: December 2017

We investigated whether loss of myocardial protection after ischemic preconditioning (IP) is related to the extent of deactivation of activated ecto-5'-nucleotidase. The coronary arteries of mongrel dogs were occluded four times for 5 min separated by 5 min of reperfusion (IP). Five (IP1), 30 (IP2), 60 (IP3), and 120 min (IP4) after the fourth 5-min coronary occlusion or after a corresponding nonischemic period (control groups), the coronary arteries were occluded for 90 min followed by 6 h of reperfusion. The infarct size-limited effect of IP gradually disappeared in the IP2 (21.6 +/- 3.9%) and IP3 (33.8 +/- 3.6%) groups compared with the IP1 group (8.3 +/- 1.6%) and returned to the control level in the IP4 group (39.9 +/- 5.2%). The increased ecto-5' -nucleotidase activity due to the IP procedure decreased according to the order of IP1 to IP4 groups. Infarct size was inversely correlated with ecto-5'-nucleotidase activity (P < 0.001). An inhibitor of ecto-5'-nucleotidase blunted the infarct size-limiting effect of IP. The infarct size-limiting effect of IP decreased as the activation of ecto-5'-nucleotidase was blunted. These results suggest that ecto-5'-nucleotidase activity plays a key role in the cardioprotection of IP.
Endothelial modulation of pH-dependent pressor response in isolated perfused rabbit lungs
Authors: Yamaguchi K. , Takasugi T. , Fujita H. , Mori M. , Oyamada Y. , Suzuki K. , Miyata A. , Aoki T. , Suzuki Y.
Published: December 2017

With the use of isolated perfused rabbit lungs (n = 152), roles of endothelium-derived relaxing factor (EDRF) in pulmonary vascular responses to hypocapnia and hypercapnia were studied. Lungs were ventilated with a gas mixture containing 1, 5, or 10% CO2 and 21% O2, adjusting the perfusate pH to 7.8, 7.4, or 7.1, respectively. Methemoglobin (MetHb), hemoglobin (Hb), methylene blue (MB), and L-argininosuccinic acid (L-ASA) were used as modulators of EDRF. To eliminate augmented shear stress, we used papaverine during hypercapnia. As a measure of EDRF, we spectrophotometrically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnia and hypercapnia evoked, respectively, unsustainable vasodilatation and vasoconstriction. Hb, MB, and L-ASA, but not MetHb, produced an increase in baseline pulmonary arterial pressure (Ppa). These agents also exacerbated vasoconstriction during hypercapnia. Hypercapnia and hypocapnia caused an increase and decrease, respectively, in EDRF production. L-ASA suppressed EDRF production in hypercapnic lungs. Papaverine did not suppress EDRF production under hypercapnia. In conclusion, 1) the effects of pH on pulmonary circulation are transient, 2) the increase in Ppa caused by hypercapnia is modulated by EDRF, and 3) the pulmonary EDRF genesis is activated by hypercapnic acidosis but suppressed by hypocapnic alkalosis.
Sympathoexcitatory and pressor responses to increased brain sodium and ouabain are mediated via brain ANG II
Authors: Huang B. S. , Leenen F. H.
Published: December 2017

Intracerebroventricular administration of hypertonic saline, ouabain, brain ouabainlike activity (OLA), or angiotensin II (ANG II) causes sympathoexcitatory and pressor effects in rats. To clarify the possible interaction between increased brain sodium, brain OLA, and the brain renin-angiotensin system (RAS), increases in mean arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) in response to intracerebroventricular 0.3 M NaCl, ouabain, and ANG II were recorded in conscious Wistar rats before and after intracerebroventricular pretreatment with the angiotensin-receptor (AT1) blocker losartan, antibody Fab fragments (Digibind), or, as control, gamma-globulins. These Fab fragments bind ouabain and brain OLA with high affinity. The arginine vasopressin (AVP) antagonist [d(CH2)5Tyr(Me)]AVP (30 micrograms/ kg) was injected intravenously before each intracerebroventricular injection. Intracerebroventricularly administered 0.3 M NaCl (3.8 mul/min for 10 min), ouabain (0.3 and 0.6 microgram), and ANG II (10 and 30 ng) caused similar pressor responses. However, the extent of HR and RSNA responses to ANG II was smaller than those to 0.3 M NaCl and ouabain. Intracerebroventricular losartan (10 and 20 micrograms) blocked responses to ANG II and 0.3 M NaCl and significantly attenuated the responses to ouabain (pressor response by 50-70%; RSNA and HR by 60-80%). In contrast, intracerebroventricular Fab fragments (66 micrograms) blocked only the responses to 0.3 M NaCl and ouabain and did not affect the responses to ANG II. These results suggest that an acute rise in brain sodium concentration increases brain OLA and the latter exerts its sympathoexcitatory and pressor effects at least partly via activation of the brain RAS.
Two-port analysis of microcirculation: an extension of windkessel
Authors: Frasch H. F. , Kresh J. Y. , Noordergraaf A.
Published: December 2017

We examined the suitability of the three-element windkessel as a reduced model of pulsatile pressure-flow relations at arteriolar and venular ends of a microcirculatory bed. Frequency domain (two-port) analysis of a distributed model of an idealized (single input, single output) microvascular network in skeletal muscle, consisting of 391 discrete vessel segments from a 20-microns-diameter arteriole to a 28-microns-diameter venule, demonstrated that the three-element windkessel is a good representation of arterial input impedance when pressure pulsations are absent at the venous end. The same model with different parameter values accounts well for venous pressure-flow relations if no pulsations occur at the arterial end. We showed that a five-element model (2 compliances, 3 resistors) provided a superior representation of pulsatile pressure-flow relations at both arterial and venous ends. Relating parameter values to known properties of the network revealed the physiological significance of the five elements. This model may prove a useful component in circulatory models incorporating both arteries and veins. While parameter values obtained herein were strictly valid for the particular microvascular network described, guidelines are provided based on physiological properties so that values may be estimated for different microvascular beds.
Uncoupling of contractile function from mitochondrial TCA cycle activity and MVO2 during reperfusion of ischemic hearts
Authors: Liu B. , el Alaoui-Talibi Z. , Clanachan A. S. , Schulz R. , Lopaschuk G. D.
Published: December 2017

In this study we determined whether contractile function becomes uncoupled during reperfusion of ischemic hearts from mitochondrial tricarboxylic acid (TCA) cycle activity or myocardial O2 consumption (MVO2). Isolated working rat hearts perfused with buffer containing 1.2 mM palmitate and 11 mM glucose were subjected to 30 min of global ischemia followed by 60 min of aerobic reperfusion. During reperfusion, cardiac work recovered to 26.5 +/- 5.4% (n = 29) of preischemic levels, even though TCA cycle activity, fatty acid beta-oxidation, glucose oxidation, glycolysis, and MVO2 rapidly recovered. As a result, the efficiency of coupling between cardiac work and TCA cycle activity and between cardiac work and mitochondrial respiration decreased during reperfusion. In contrast, coupling of TCA cycle activity to MVO2 during reperfusion recovered to preischemic values. Addition of 1 mM dichloroacetate at reperfusion resulted in a significant increase in both cardiac work and cardiac efficiency during reperfusion. This was associated with a significant decrease in H+ production due to an improved balance between glycolysis and glucose oxidation. These data demonstrate that mitochondrial function and overall myocardial ATP production quickly recover in rat hearts after a 30-min period of global ischemia. However, mitochondrial ATP production is not efficiently translated into mechanical work during reperfusion. This may be due to an imbalance between glycolysis and glucose oxidation, resulting in an increase in H+ production and a decrease in cardiac efficiency.