bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of adenosine in hyperemic response of coronary blood flow in microembolization
Authors: Hori M. , Inoue M. , Kitakaze M. , Koretsune Y. , Iwai K. , Tamai J. , Ito H. , Kitabatake A. , Sato T. , Kamada T.
Published: December 2017

To investigate the pathophysiology of acute embolization of small coronary vessels and the role of adenosine in this abnormality, regional coronary blood flow (CBF), coronary vascular resistance, arteriovenous O2 difference, lactate extraction ratio, and adenosine release were studied in 39 anesthetized open-chest dogs after acute coronary embolization with microspheres of three different diameters (15 +/- 1, 94 +/- 8, and 293 +/- 23 microns). In 16 dogs, the left anterior descending coronary artery was embolized by repetitive injections of 15-microns microspheres, up to 4.4 +/- 0.4 X 10(5)/g myocardium; at this point CBF, determined by the electromagnetic flowmeter at the proximal site of the artery, was reduced toward zero. Up to 37% of total embolization, resting CBF increased to 175 +/- 36% of control; thereafter it decreased almost linearly as the extent of embolization was increased. After embolization, coronary arteriovenous O2 difference was significantly (P less than 0.01) decreased with a marked release of adenosine in the coronary vein. Despite a hyperemic flow response of CBF in the embolized area, myocardial ischemia was not prevented; maximal increase in CBF after 100-microns microsphere embolization (141 +/- 11% of control CBF, n = 6) was significantly (P less than 0.05) less than that in 15-micron microsphere embolization, whereas 300-microns microsphere embolization minimally increased CBF (123 +/- 13%, P greater than 0.1; n = 5). Hyperemic flow remained unchanged for at least 3 h when adenosine was persistently released. Theophylline significantly attenuated this response. These results indicate that in embolization with microspheres less than 300 microns in diameter, hyperemic response of coronary blood flow occurs, probably due to the hyperemia of nonoccluded vessels in the adjacent area of ischemic foci to adenosine released from the ischemic myocardium.
Construction of a multipolar electrode system referenced and anchored to endocardium for study of arrhythmias
Authors: Worley S. J. , Smith W. M. , Ideker R. E.
Published: December 2017

We developed a Teflon plunge electrode system (Teflon plunge) with important advantages over currently used electrodes. The Teflon plunge consists of an anchor-introducer (anchor) attached to the tip of an 0.8-mm diam epoxy-filled Teflon tube supporting six bipolar recording sites. The plunge is inserted through the myocardium into the ventricular cavity perpendicular to the epicardium. Once in the left ventricular cavity the anchor at the tip of the plunge pivots perpendicular to the long axis of the plunge and seats on the endocardium. It is maintained in position with a 4-0 nylon line (line) that extends from its attachment to the anchor through the body of the plunge to the epicardial end where it is secured with a Ligaclip. Thus the electrode contacts are placed a predetermined distance from the endocardium. When the Ligaclip is released, the plunge is removed from the heart leaving the line in the track of the electrode attached to the anchor as a marker for histological studies. The Teflon plunge will facilitate the evaluation of the role of the endocardium in ventricular arrhythmias by locating recording sites a stable, known distance from the endocardium and by marking the electrode track for histological studies.
Vagally mediated regulation of renal function in conscious primates
Authors: Vatner S. F. , Manders W. T. , Knight D. R.
Published: December 2017

The effects of vagal denervation (VD) were examined on responses of Na+ and water excretion to acute volume expansion (18 ml/kg of 6% dextran in saline) in six conscious rhesus monkeys with chronic sinoaortic denervation (SAD). After SAD, volume expansion increased mean arterial pressure (from 95 +/- 6.6 to 119 +/- 7.5 mmHg), right atrial pressure (from 1.3 +/- 0.7 to 5.9 +/- 1.8 mmHg), urine flow (from 0.08 +/- 0.01 to 0.68 +/- 0.20 ml/min), and Na+ excretion (from 1.30 +/- 0.45 to 29.51 +/- 10.40 mueq/min). After VD, volume expansion increased mean arterial and right atrial pressures similarly, but induced significantly lower (P less than 0.05) increases in urine flow (from 0.05 +/- 0.01 to 0.19 +/- 0.03 ml/min) and Na+ excretion (from 0.87 +/- 0.27 to 11.50 +/- 6.13 mueq/min). Thus vagal mechanisms appear to play an important role in mediating excretion of Na+ and water in response to acute volume expansion in the conscious primate.
Effects of digitalis intoxication on pacemaker rhythm and synchronization in rabbit sinus node
Authors: Takayanagi K. , Jalife J.
Published: December 2017

Toxic doses of digitalis can induce severe arrhythmias in the sinus node. Since digitalis is known to induce electrical uncoupling in heart tissues, it is possible that the arrhythmias may be mediated by cell-to-cell uncoupling leading to desynchronization of pacemaker cells. We investigated this possibility using intracellular recordings and two different preparations of isolated rabbit sinus node. First, the whole sinus node region with the crista terminalis and a portion of right atrium were exposed to 2 microM ouabain in the presence of atropine (0.09 microM) and propranolol (0.77 microM). With ouabain superfusion, there was a gradual increase in spontaneous discharge, conduction delay, pacemaker shifts, and arrhythmias associated with multiple pacemaker sites. Interaction between pacemakers rapidly decreased, and finally atrial arrest was observed. Second, thin strips of sinus node were placed in a three-compartment bath. Superfusion of the central segment (1.0-1.5 mm) with 1-5 microM ouabain led to tachycardia and apparent conduction delay, followed by asynchronous firing and phasic interactions between pacemakers across the central segment. These interactions diminished in the course of intoxication, indicating a gradual increase of electrical uncoupling induced by the drug. All effects were reversible on washout. We conclude that digitalis-induced arrhythmias in the sinus node result from cell-to-cell uncoupling and loss of synchrony between pacemaker cells. The pattern of arrhythmias can be predicted by the phasic interactions between the pacemakers.
Adenosine deaminase attenuates canine coronary vasodilation during systemic hypoxia
Authors: Merrill G. F. , Downey H. F. , Jones C. E.
Published: December 2017

The hypothesis that adenosine mediates the coronary vasodilatory response to hypoxia was tested by determining if intracoronary infusion of the adenosine degrading enzyme, adenosine deaminase (ADA), would attenuate this response. Efficacy of ADA was also evaluated by examining its effect on the coronary responses to exogenous adenosine and to 20-s myocardial ischemia. Experiments were conducted in 14 anesthetized, open-chest dogs ventilated 3-5 min with 3% O2-5% CO2-92% N2 to induce systemic hypoxia. Under control, pre-ADA conditions, hypoxia (arterial PO2 19 +/- 2 mmHg) caused left anterior descending (LAD) coronary blood flow to increase from 100 +/- 12 to 382 +/- 47 ml X min-1 X 100 g-1 (+282%). After infusion of ADA (5 U X kg-1 X min-1 for 8-10 min) into the LAD, equally severe hypoxia (arterial PO2 18 +/- 3 mmHg) caused a significantly smaller increase in LAD flow, 79 +/- 9 to 234 +/- 41 ml X min-1 X 100 g-1 (+195%). Oxygen consumption in the LAD perfusion field was unchanged by hypoxia before ADA but fell significantly during hypoxia after ADA. ADA also attenuated significantly the coronary vasodilatory response to exogenous adenosine and to 20-s ischemia. The results of this investigation demonstrate a significant role of adenosine in the coronary vasodilatory response to systemic hypoxia.
Influence of exogenously generated oxidant species on myocardial function
Authors: Blaustein A. S. , Schine L. , Brooks W. W. , Fanburg B. L. , Bing O. H.
Published: December 2017

Oxygen-derived free radicals (OFR) have been implicated as mediators of tissue injury in various disease states. Their participation in myocardial injury due to ischemia-reperfusion has also been suggested. To characterize the mechanical dysfunction associated with OFR-induced injury, we studied alterations in isometric contractions of rat papillary muscle at 28 degrees C. A purine-xanthine oxidase system was used to generate OFR. Neither purine nor xanthine oxidase alone had significant effects on rest or active tension, duration of the contraction, or peak rates of tension development or decline. In contrast, their combination resulted in a reduction of active tension to 38% of base-line values without alteration in rest tension. This reduction was largely due to a decline in the peak rate of tension development. When catalase or superoxide dismutase was introduced into the bath prior to the generation of OFR, catalase but not superoxide dismutase offered essentially complete functional protection. These results substantiate that impaired myocardial function can result from exposure to OFR. In this case the active radicals appear to be either peroxides or hydroxyl and not superoxide. These observations provide a basis for understanding the functional protection afforded ischemic myocardium by OFR scavenging enzymes.
Postrest inotropy in rabbit ventricle: Na+-Ca2+ exchange determines sarcoplasmic reticulum Ca2+ content
Authors: Sutko J. L. , Bers D. M. , Reeves J. P.
Published: December 2017

To determine whether Na+-Ca2+ exchange is a physiologically significant Ca2+ efflux mechanism in rabbit ventricle, we investigated the effects exerted on postrest contractions by interventions that alter the transmembrane distribution of Na+ or Ca2+ so as to retard Ca2+ efflux via this system. Contractions elicited after rest periods of 0.25-10 min in duration were studied. The following interventions increased postrest contractions much more than those elicited by rhythmic stimulation: 1) Na+ pump inhibition by cardiac glycosides or by a reduction in extracellular K+, 2) reduction of extracellular Na+ (maintaining a constant [Ca2+]-to-[Na+]2 ratio), and 3) elevation of extracellular Ca2+. In contrast, isoproterenol, norepinephrine, and histamine produced comparable increases in both rhythmically stimulated and postrest contractions, suggesting that the postrest contractile potentiation was not just the result of a general increase in inotropic state. Ryanodine, which appears to antagonize sarcoplasmic reticulum (SR) Ca2+ release in cardiac muscle, markedly reduced the amplitude of the postrest contractions, but only modestly decreased rhythmically stimulated responses. Results suggest 1) that Ca2+ released from SR is involved in postrest response, 2) that Na+-Ca2+ exchange serves as a Ca2+ efflux pathway in normally polarized resting rabbit ventricle, and 3) that this activity in part determines the amount of Ca2+ available for release from SR.
Enhanced response of arterioles to oxygen during development of hypertension in SHR
Authors: Lombard J. H. , Hess M. E. , Stekiel W. J.
Published: December 2017

The goal of this study was to assess the possible role of O2-related local control mechanisms in contributing to an elevated skeletal muscle resistance during the development of hypertension in the spontaneously hypertensive rat (SHR). Diameters of first- (1A), second- (2A), third- (3A), and fourth-order (4A) arterioles were measured by television microscopy in the cremaster muscle of SHR in the early (4- to 6-wk-old) and rapidly developing (8- to 9-wk-old) stages of hypertension and in age-matched normotensive Wistar-Kyoto (WKY) controls. Active neurogenic tone was blocked by superfusing the tissue with 0.1 microgram/ml tetrodotoxin. When superfusion solution PO2 was elevated by changing the gas equilibration mixture from 0 to 5% O2, neurally blocked 3A and 4A of SHR exhibited a significantly greater constriction and a higher incidence of complete closure than those of their age-matched WKY controls. However, there were no significant differences in the constriction of larger arterioles (1A and 2A) in response to elevated superfusion solution PO2. The results suggest that O2-related local control mechanisms could contribute to constriction and closure of small arterioles and to an elevated skeletal muscle vascular resistance early in the development of hypertension in SHR
Periodic cutaneous blood flow during postocclusive reactive hyperemia
Authors: Wilkin J. K.
Published: December 2017

Forearm cutaneous blood flow was monitored continuously by laser Doppler velocimetry in 10 normal human subjects before, during, and after external brachial artery occlusion for 6 min duration. During the reactive hyperemic response, the cutaneous blood flow exhibited rhythmic oscillatory activity. The amplitude of the oscillations was maximum 30 s postocclusion. Thereafter, the amplitude of the oscillations declined until cutaneous blood flow returned to control values. The mean (+/- SEM) period for the oscillations was 9.26 +/- 0.30 s. Bilateral forearm sites were examined simultaneously in eight studies and demonstrated a progressive loss of synchronicity. Nine additional studies were performed in which two forearm sites only 1.8 cm apart demonstrated a progressive loss of synchronicity resulting from different periodicities of microcirculatory flow patterns. These oscillations in cutaneous blood flow, which occur during postocclusive reactive hyperemia as a normal physiological phenomenon, are not synchronous in adjacent areas of skin. The data suggest an origin of the oscillations in the cutaneous vasculature that is either unrelated to sympathetic vasoconstrictor influences or is due to nonuniform cutaneous sympathetic excitation.
Antagonism of forskolin effects by adenosine in isolated hearts and ventricular myocytes
Authors: West G. A. , Isenberg G. , Belardinelli L.
Published: December 2017

Adenosine is known to antagonize the effects of catecholamine stimulation in atrial and ventricular tissue; however, its mechanism of action is unknown. Forskolin is an inotropic agent that causes an increase in cyclic AMP (cAMP) levels independent of receptor stimulation. We sought to test whether adenosine could attenuate the effects of forskolin in isolated perfused guinea pig hearts and isolated single ventricular myocytes. In isolated perfused hearts (n = 18), forskolin caused a concentration-dependent increase in left ventricular pressure and dP/dt. Adenosine (5 microM) antagonized the forskolin (0.35 microM)-induced increase in left ventricular pressure and dP/dt by 96 +/- 2 and 92 +/- 4% (means +/- SE), respectively. In contrast, in four hearts, adenosine was ineffective in attenuating the inotropic response to dibutyryl cAMP. In isolated ventricular myocytes (n = 10) 150 nM forskolin caused a significant increase in action potential duration and plateau. In voltage-clamp experiments (n = 8), 150 nM forskolin caused a 39 +/- 3% increase in the calcium current, which was antagonized by adenosine (50 microM) by 80%. Forskolin also caused an increase in contractility, as estimated by sarcomere shortening of the cell. Adenosine, and its analogue N6-R-phenylisopropyladenosine (L-PIA), antagonized the effects of 150 nM forskolin on the action potential and on sarcomere shortening. Dibutyryl cAMP had similar effects as forskolin, but they were not antagonized by adenosine. At higher concentrations of forskolin, above 300 nM, delayed after depolarizations and sustained spontaneous activity occurred that could be abolished by L-PIA. Forskolin caused a concentration-dependent increase in cAMP, measured in isolated ventricular myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of hypoxia and hypercapnia on ACE activity in the cerebral microcirculation of anesthetized dogs
Authors: Pitt B. R. , Lister G. , Dawson C. A. , Linehan J. H.
Published: December 2017

Angiotensin-converting enzyme (ACE) activity of the cerebral microcirculation of anesthetized dogs was measured from cerebral venous outflow curves after bolus injection of a synthetic ACE substrate, [3H]benzoyl-phenylalanyl-alanylproline ([3H]BPAP), into a common carotid artery. Cerebral BPAP metabolism was quantified by measuring the concentration of [3H]benzoyl-phenylalanine (the product of BPAP hydrolysis by ACE) in blood samples from the sagittal sinus after occlusion of the lateral sinuses with bone wax. Instantaneous BPAP metabolism in each sample increased as a function of time after injection, suggestive of perfusion heterogeneity, and averaged 59 +/- 4% (n = 8) over a single pass during normoxia and normocapnia. The ratio of Vmax (the maximal rate of cerebral BPAP metabolism) to Km (the concentration at Vmax/2), was calculated from instantaneous outflow curves using a model based on first-order kinetics. Increases in cerebral blood flow during either hypoxia or hypercapnia significantly reduced BPAP metabolism to 33 +/- 3 (n = 7) and 24 +/- 3% (n = 5), respectively; however, Vmax/Km of ACE activity (0.19 +/- 0.03 ml/s) was not affected by either condition. The lack of change in apparent kinetics of ACE activity (i.e., in Vmax/Km) during hypoxia or hypercapnia suggests that recruitment of cerebral capillaries was not a quantitatively significant factor in controlling BPAP metabolism with this degree of either hypoxia or hypercapnia.
Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor
Authors: Rubanyi G. M. , Vanhoutte P. M.
Published: December 2017

Experiments were designed to determine the effects of oxygen-derived free radicals on the production and biological activity of endothelium-derived relaxing factor or factors released by acetylcholine. Rings of canine coronary arteries without endothelium (bioassay rings) were superfused with solution passing through a canine femoral artery with endothelium. Superoxide dismutase caused maximal relaxation of the bioassay ring when infused upstream, but not downstream, of the femoral artery; this effect of superoxide dismutase was inhibited by catalase. Infusion of acetylcholine relaxed the bioassay rings because it released a labile relaxing factor (or factors) from the endothelium. When infused below the femoral artery, superoxide dismutase and, to a lesser extent, catalase augmented the relaxations to acetylcholine. Superoxide dismutase, but not catalase, doubled the half-life of the endothelium-derived relaxing factor(s). This protective effect of the enzyme was augmented fivefold by lowering the oxygen content of the perfusate from 95 to 10%. These data demonstrate that: superoxide anions inactivate the relaxing factor(s) released by acetylcholine from endothelial cells and hyperoxia favors the inactivation of endothelium-derived relaxing factor(s).
Diameter and blood flow of skeletal muscle venules during local flow regulation
Authors: House S. D. , Johnson P. C.
Published: December 2017

Whole organ studies suggest that venous resistance increases as blood flow falls and decreases when blood flow increases. In experiments on skeletal muscle we tested the hypotheses that these resistance changes may be due to changes in venous diameter, changes in the number of venules with blood flow, and/or changes in the shear rate of blood in venules. The hypotheses were tested by measuring diameter and red cell velocity in cat sartorius muscle venules (7–200 microns diam) during arterial pressure reduction and muscle contraction. There was no observable change in venular diameter and an insignificant change in the number of venules with blood flow during these perturbations. There was a significant decrease in the normalized velocity (bulk velocity/vessel diameter) of blood from a mean of 13 s-1 under control conditions to 5 s-1 during arterial pressure reduction to 20 mmHg. Combining these blood velocity data with published in vivo viscosity data, it is deduced that apparent blood viscosity in venules would increase 100% when blood flow was reduced 60%. During postcontraction hyperemia the normalized velocity of blood in venules increased from 16 to 38 s-1, suggesting that apparent blood viscosity in venules would fall 54%.
Thyroidectomy of SHR: effects on ventricular relaxation and on SR calcium uptake activity
Authors: Rodgers R. L. , Black S. , Katz S. , McNeill J. H.
Published: December 2017

Ventricular hypertrophy and hypothyroidism are each characterized by impaired cardiac muscle relaxation and sarcoplasmic reticulum (SR) calcium uptake activity. A previous report also showed that hypothyroidism does not reverse ventricular hypertrophy (left-to-right ventricular weight ratios) of spontaneously hypertensive rats (SHR). We characterized the effects of thyroidectomy of 8 wk duration on relaxation of ejecting hearts and on SR calcium uptake activity from SHR and nonhypertrophic Wistar-Kyoto rat (WKY) controls. Relaxation was quantified by plotting maximum left ventricular pulse pressure (Pmax) vs. the area under the falling phase of the left ventricular pressure wave at three different pressure loads. Ventricles of euthyroid SHR were characterized by impaired relaxation and depressed SR calcium uptake activity compared with those of euthyroid WKY, confirming earlier studies. Thyroidectomy reduced ventricular relaxation and SR calcium uptake activities to about the same extent in SHR and WKY strains so that these measurements were most depressed in the SHR hypothyroid group. When all groups were considered, the extent of mechanical relaxation ex vivo and the rate of SR calcium uptake in vitro were well correlated.
Enhanced adrenergic constriction of iliac artery with removal of endothelium in conscious dogs
Authors: Young M. A. , Vatner S. F.
Published: December 2017

We studied, in conscious dogs, the effects of removal of endothelium on the responses of iliac artery diameter and iliac blood flow to intra-arterial infusions of adrenergic agonists. With endothelium intact, iliac diameter increased with intra-arterial infusion of nitroglycerin (4.7 +/- 0.4%), acetylcholine (4.2 +/- 0.6%), and epinephrine (4.5 +/- 1.3%), and decreased with norepinephrine (-7.5 +/- 1.7%), phenylephrine (-6.6 +/- 1.0%), and B-HT 920 (-2.1 +/- 0.6%). One- to-five days following removal of endothelium with a balloon-tipped catheter, base-line iliac diameter was unchanged, and still increased with nitroglycerin (4.6 +/- 0.5%), but not with acetyl-choline, and epinephrine actually decreased diameter (-3.5 +/- 1.3%). Removal of the endothelium also enhanced the constriction observed with norepinephrine (-12.5 +/- 2.0%) and phenylephrine (-11.4 +/- 1.6%), but not with B-HT 920 (-1.8 +/- 0.5%). The changes in arterial pressure, iliac blood flow, iliac vascular resistance, and heart rate induced by any of the agonists did not differ before and after removal of the endothelium. These results indicate that the endothelium mediates the dilation in response to epinephrine and also serves an important role in protecting against alpha 1-adrenergic vasoconstriction of large iliac arteries.
Adenosine's role in regulating basal coronary arteriolar tone
Authors: Gewirtz H. , Olsson R. A. , Brautigan D. L. , Brown P. R. , Most A. S.
Published: December 2017

This study examined the role of adenosine in regulating coronary arteriolar tone under basal conditions in the normal coronary circulation. Measurements of hemodynamics and flow (microspheres) were made in eight closed-chest, sedated pigs at 1) control and 2) after 10 min of infusion of adenosine deaminase (ADA, 10 U X kg-1 X min-1) into the left anterior descending (LAD) coronary artery. Heart rate was held constant by atrial pacing. Transmural flow in the distal LAD zone did not change versus control (1.81 +/- 0.36) with ADA (1.78 +/- 0.46). However, in comparison with control the distal LAD:circumflex zone transmural flow ratio (0.96 +/- 0.04) declined (P less than 0.01) during ADA infusion (0.93 +/- 0.04). Similarly, the distal LAD:circumflex zone transmural flow resistance ratio increased significantly (P less than 0.01) versus control (1.04 +/- 0.05) in response to intracoronary ADA infusion (1.08 +/- 0.04). Regional myocardial oxygen consumption in the distal LAD zone did not change versus control (16.9 +/- 3.3 3.3 ml X min-1 X 100 g-1) during ADA (16.9 +/- 4.5). Additional studies in 15 open-chest swine given intracoronary infusion of ADA demonstrated that 1) the enzyme penetrates the interstitial fluid (ISF) and 2) attains ISF levels which are adequate to reduce basal adenosine concentration 10 fold even if substantial increase in adenosine production occurs in response to ADA. Thus, since destruction of adenosine by ADA caused only very modest relative reduction in regional flow, it is likely that the nucleoside plays only a limited role in regulation of arteriolar tone under basal conditions in the normal coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of fatty acid on performance and lipid content of hearts from diabetic rabbits
Authors: Fields L. E. , Daugherty A. , Bergmann S. R.
Published: December 2017

The relationship of external work to exogenous substrate supply and whole heart lipid content was studied in hearts isolated from 27 normal and 24 alloxan-diabetic rabbits. In addition, we evaluated hearts from seven rabbits after 4 days of untreated diabetes followed by 10 days of insulin therapy. Hearts were retrogradely perfused with erythrocyte-enriched modified Krebs-Henseleit media in which glucose, palmitate, and insulin were present in concentrations simulating diabetic plasma (13 mM, 0.4 mM, and 15 microU/ml, respectively). Diabetes was associated with a greater than 40% reduction in peak left ventricular systolic pressure, dP/dtmax, and left ventricular pressure-time index (P less than 0.01 for each). Perfusion of hearts from six diabetic animals with low concentrations of exogenous fatty acid (0.06 mM) normalized left ventricular (LV) performance. Insulin therapy also completely normalized LV performance. This improvement was associated with lower heart fatty acid and triacylglycerol content. These studies suggest that the myocardial dysfunction in hearts from rabbits with alloxan-induced diabetes of 2-wk duration may be, in part, due to enhanced sensitivity to deleterious effects of high exogenous levels of fatty acid.
Right atrial volume during hemorrhage in the dog
Authors: Carlson D. E. , Burchard K. W. , Gann D. S.
Published: December 2017

Atrial B receptors elicit reflex changes after hemorrhage and respond to changes in atrial volume, but the latter have not been measured after hemorrhage. An impedance catheter that was originally designed to measure ventricular volume was advanced into the atrium from the femoral vein in each of 10 splenectomized dogs that were anesthetized with alpha-chloralose. The rate of hemorrhage and reinfusion was 2% of the estimated blood volume per min. Cardiac output (CO) was measured with dye dilution. The components of the atrial volume signal that were most sensitive to hemorrhage were the filling that occurred during late ventricular systole (Vs) and the absolute volume at the end of ventricular systole, (Vabs). Both variables were significantly less than base line (P less than 0.05) after 10% hemorrhage. The rate of change of Vs decreased significantly after 20% hemorrhage. However, the volume ejected with each atrial beat (Ve) decreased significantly (P less than 0.05) only after 30% hemorrhage. Atrial output (AO) as computed by multiplying Ve by heart rate (HR) did not change after hemorrhage. The ratio of AO to CO increased in direct proportion to HR (P less than 0.01) so that after 30% hemorrhage, for which HR was high, the decreases in CO from base line in individual dogs correlated significantly with the changes in AO (P less than 0.01). Since the B receptors are known to fire at the end of the ventricular systole at a rate that is dependent on blood volume, their firing may be a function of the concomitant atrial signals, Vs and Vabs, that are most sensitive to blood volume, and these atrial signals may serve as indexes of B fiber activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Feline left ventricle does not always operate at optimum power output
Authors: van den Horn G. J. , Westerhof N. , Elzinga G.
Published: December 2017

In a previous study we showed that under a variety of conditions the feline left ventricle operates at optimum external power. This condition was defined as matching. In the present study matching of left ventricle and systemic arterial tree has been further investigated in the open-thorax cat during control, after volume loading (n = 8), and during norepinephrine infusion (n = 8). The pump-function graph relating mean left ventricular pressure and mean flow was fitted with a parabola characterized by two parameters, the pressure axis and the flow axis intercepts (Pmax and Fmax, respectively). After volume loading, as well as during norepinephrine infusion, the pump-function graph showed an outward shift plus a clockwise rotation. Pmax and Fmax increased 27 and 8% during volume loading and 37 and 8% during norepinephrine. In the steady states the mean flows at the working point and at the point of optimum external power were determined. During control and volume loading these flow values could not be shown to differ. However, during norepinephrine infusion, flow at the working point was found to be smaller than at optimal external power. This finding implies that during norepinephrine, the left heart does not operate at optimum external power; so a mismatch of heart and periphery is obtained.
Myocardial flow during tachycardia in dogs with chronic left ventricular hypertrophy
Authors: Rembert J. C. , Greenfield J. C.
Published: December 2017

The effect of pacing-induced tachycardia on transmural myocardial blood flow distribution was studied in 16 awake dogs with left ventricular hypertrophy secondary to modified aortic coarctation banding done at 7-10 wk of age. They were studied between 11 and 50 mo of age. In those dogs with mild and moderate left ventricular hypertrophy, the blood flow distribution was normal during resting conditions and remained normal during an increased heart rate of 250 beats/min. In the six dogs with severe hypertrophy (left ventricle/body wt greater than 7.0 g/kg) a reduced flow to the endocardial layers was present during resting conditions (endocardial/epicardial 0.91 +/- 0.09), but during tachycardia the endocardial-to-epicardial ratio normalized to 1.26 +/- 0.08 (mean +/- SEM). These data indicate that, in dogs with significant left ventricular hypertrophy, the vasoregulator mechanism functions adequately to maintain normal transmural myocardial blood flow distribution during tachycardia. In addition, studies were carried out to compare the magnitude of hypertrophy with the hemodynamic load secondary to coarctation banding.
Pulse-wave model of brachial arterial pressure modulation in aging and hypertension
Authors: Chadwick R. S. , Goldstein D. S. , Keiser H. R.
Published: December 2017

We apply a pulse-wave theory to a model of the human arm arterial system that predicts the changes in the arterial pressure waveform as it traverses the vasculature (increased pulse pressure, sharper main wave, disappearance of the aortic incisura, and appearance of a diastolic dicrotic wave) and also predicts the observed modulation of the waveform during phenylephrine-induced vasoconstriction and nitroglycerin-induced vasodilation. The model considers the arm arterial system as a tapered, distensible tube that bifurcates and then ends in a loop, with sidebranch networks represented by distributed Windkessels. The model uses verifiable values for realistic parameters. We found that the vertical modulation of the dicrotic wave, in humans, decreased with advancing age and with high blood pressure. The model explained these findings in terms of increasing vascular rigidity and decreasing small vessel vasodilator responsiveness. We noted a significant negative correlation between the arterial level of plasma norepinephrine and the amount of modulation of the dicrotic wave after nitroglycerin among subjects 40 yr old or younger, suggesting a sympathetic neurogenic contribution to the vascular abnormalities observed in relatively young patients with essential hypertension.
Two neural mechanisms in rat fastigial nucleus regulating systemic and cerebral circulation
Authors: Mraovitch S. , Pinard E. , Seylaz J.
Published: December 2017

We have studied in anesthetized (alpha-chloralose) and paralyzed (d tubocurarine) rats the effects of electrical stimulation of the fastigial nucleus (FN) on local cerebral blood flow (lCBF) and its relationship to intracerebral PO2, and PCO2 and to the systemic arterial pressure (Pa). Mass spectrometry was used to measure quantitatively lCBF (repetitively) and cerebral PO2 and PCO2 (continuously). A systematic exploration of the FN for an increase in Pa and/or lCBF revealed that the most active sites for the rise in Pa were localized within the rostral FN, while those that elicited an increase in lCBF were found throughout the rostrocaudal extent of the FN. The increase in lCBF elicited from the caudal FN was not associated with changes in Pa. The increase in lCBF was concomitant with an increase in intracerebral PO2 and a slight decrease in PCO2. Although the increases in Pa and lCBF were dependent on stimulus frequency, their frequency-response curves were different. We conclude that 1) in contrast to the neurons or fibers of passage of the rostral FN, which mediate an increase in Pa, the neurons or fibers of passage that elicit changes in lCBF are localized along the rostrocaudal axis of the FN; 2) changes in the local gas partial pressures are not responsible for the vasodilation observed; and 3) the cerebral vasodilation and systemic vasoconstriction evoked by FN stimulation are probably mediated by two different neural mechanisms.
Vagal regulation of arginine vasopressin in conscious dogs
Authors: Morita H. , Manders W. T. , Skelton M. M. , Cowley A. W. , Vatner S. F.
Published: December 2017

To determine whether removal of inhibition of arginine vasopressin (AVP) by vagal afferents results in persistent elevation of plasma AVP, effects of bilateral cervical vagal denervation (VD) on plasma AVP were examined in 10 dogs with sinoaortic baroreceptor denervation (SAD). VD increased plasma AVP levels by 98 +/- 16 from 3.8 +/- 1.0 pg/ml (P less than 0.01) at 15 min after VD. By 4 h after VD there were no significant differences from control values. Responses of plasma AVP were also examined in response to acute volume expansion in conscious dogs with all reflexes intact, SAD, and SAD plus VD. In intact and SAD dogs, when blood volume was expanded by 20% with a rapid infusion of isotonic, isooncotic 3% dextran in saline, mean left atrial pressure rose transiently and plasma AVP fell insignificantly. With more prolonged stimulation to cardiopulmonary receptors, i.e., when left atrial pressure was maintained at elevated levels for 1 h by volume loading, plasma AVP fell by 0.9 +/- 0.3 pg/ml. However, after correction for hemodilution was made, AVP did not change with volume expansion, indicating that secretion rate was unchanged. Thus acute, but not chronic, interruption of vagal pathways induces striking release of AVP, but a resetting mechanism rapidly returns plasma AVP to control levels. Furthermore, stimulation of vagally innervated receptors by means of acute volume expansion suppresses plasma AVP when the elevation in atrial pressure is sustained, but this fall in plasma AVP can be accounted for entirely by the concomitant hemodilution.
Excretion of artifactual endogenous digitalis-like factors
Authors: Kelly R. A.
Published: December 2017

Radioimmunoassays have been used to detect digoxin-like immunoreactive factors (DLF) in the plasma and urine of hypertensive patients and rats with deoxycorticosterone acetate (DOCA)-salt hypertension. Uninephrectomized rats (n = 9), given 15 mg DOCA . kg-1 . wk-1, were fed a standard rat chow supplemented with 2% NaCl (DOCA-HS); control animals (n = 15) were given vehicle injection and a specially formulated low-salt diet (0.05% NaCl). At 4 wk, DOCA-HS rats were hypertensive (121.4 +/- 10.1 vs. 88 +/- 4.4 Torr, mean +/- SEM, P less than 0.05) and excreted more DLF (2.7 +/- 1.1 vs. 0.2 +/- 0.1 ng digoxin equivalents . day-1, P less than 0.001) compared with control rats. DLF, partially purified from DOCA-HS urine by antidigoxin antibody immunoaffinity chromatography, was found to have a molecular weight less than 2,000, was resistant to acid hydrolysis or proteases, and had many properties of the cardiac glycosides, including inhibition of Na+-K+-ATPase activity, displacement of ouabain from human erythrocyte membranes, and inhibition of 86Rb influx into red blood cells. When DOCA-HS rats were switched to the low-sodium chow, DLF excretion dropped precipitously. No measurable DLF (less than 10 pg/ml) was detected in the plasma of rats eating either chow. However, greater than 95% of the urinary DLF could be attributed to a contaminant in the standard laboratory chow; rats fed the low-salt chow supplemented with 2% NaCl excreted much less DLF, and DLF was isolated from the standard chow.(ABSTRACT TRUNCATED AT 250 WORDS)
Isoproterenol directly stimulates the Na+-K+ pump in isolated cardiac myocytes
Authors: Desilets M. , Baumgarten C. M.
Published: December 2017

It has been suggested that catecholamines directly stimulate Na+-K+ pump activity in heart; however, these studies on multicellular preparations are confounded by possible alterations of extracellular K+ concentrations ([K+]o). We reinvestigated this problem by studying the effect of the beta-agonist isoproterenol (Iso) on intracellular Na+ activity (aiNa) in ventricular myocytes enzymatically isolated from rabbit heart. In 5 mM [K+]o, 0.1 microM Iso caused a 24.6 +/- 2.0% decrease of aiNa. Exposure to 1 microM Iso only caused a small additional decrease (27.8 +/- 2.4%), while a diminution of aiNa could already be noticed with only 10 nM Iso (12.8 +/- 1.9% diminution). Myocytes superfused with 15 mM [K+]o also exhibited a significant decrease of aiNa (22.9 +/- 3.6%) when exposed to 0.1 microM Iso. These data argue that accumulation of external K+ does not account for the effect of Iso on steady-state aiNa as postulated by Gadsby (Nature Lond. 306: 691-693, 1983). Furthermore, aiNa in myocytes superfused with 1.5 mM [K+]o decreased by only 8.7% on addition of 0.1 microM Iso. The latter observation suggests that the beta-agonist effect on aiNa regulation is directly or indirectly dependent on membrane potential and/or aiNa. Finally, kinetic analysis of the effect of 1 microM Iso on the decrease in aiNa on changing [K+]o from 1.5 to 5 mM demonstrated that the time course of aiNa recovery was accelerated by a factor of 1.9. This readily suggests that active Na+ transport is directly stimulated by Iso. The much greater relative effect of Iso on the time constant than on steady-state aiNa further indicates that Iso may also increase passive Na+ influx.
Dissociation of adenosine from metabolic regulation of coronary flow in the lamb
Authors: Downing S. E. , Chen V.
Published: December 2017

The objective of these studies was to evaluate the contribution of an adenosine mechanism to metabolic regulation of coronary flow. Cardiac O2 metabolism (MVO2) was altered by changing cardiac output while aortic pressure and heart rate were held constant (paced). Ganglionic (tetraethylammonium chloride) and beta blockade (propranolol) were employed. Relationships of coronary flow to MVO2 were determined in control and alloxan diabetic animals. The latter have previously been shown to have reduced sensitivity to adenosine [Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H252-H258, 1982]. In each group, responses were measured before and after adenosine receptor blockade with aminophylline (10 mg/kg). Responses to infused adenosine were also compared. A linear relationship between adenosine infusion rate and flow was found in all conditions. Aminophylline caused a 70% reduction in adenosine sensitivity in controls. In the diabetics, adenosine sensitivity was much reduced and was identical with blocked controls. A close correlation between left ventricular work and MVO2 was found in both groups. Coronary flow increased linearly with MVO2, and the slopes before and after aminophylline were identical. Myocardial O2 extraction remained unchanged. The same relationships were found in the diabetics, and responses did not differ from controls. Thus, in two conditions of sharply reduced sensitivity to exogeneous adenosine, coronary flow (and resistance) were as equally well matched to MVO2 as in controls. These data suggest that mechanisms other than, or in addition to, adenosine provide the close link between MVO2 and coronary flow with changing cardiac work loads.
Role of O2-hemoglobin affinity in the regulation of cerebral blood flow in fetal sheep
Authors: Rosenberg A. A. , Harris A. P. , Koehler R. C. , Hudak M. L. , Traystman R. J. , Jones M. D.
Published: December 2017

Cerebral blood flow (CBF) and cerebral O2 transport (CBF X arterial O2 content) in the fetal sheep are nearly twice that in the adult, despite similar rates of cerebral O2 utilization. We tested the hypothesis that the difference depends on the increased oxyhemoglobin affinity in the fetus, using P50 (PO2 at which hemoglobin is 50% saturated) as the index of oxyhemoglobin affinity. We studied 18 unanesthetized fetal sheep in utero. In six animals the P50 was raised from 16.6 +/- 1.2 (SD) mmHg to 31.7 +/- 4.7 mmHg by exchange transfusing the fetus with adult sheep red blood cells. We measured CBF (with radioactive microspheres) and the PO2, PCO2, pH, and O2 content in carotid artery and sagittal sinus blood twice at the original P50 and twice after exchange transfusion. Arterial O2 content fell significantly at the higher P50. Since the fall in O2 content was not accompanied by a corresponding rise in CBF, O2 transport fell by 45%. Cerebral O2 consumption (CMRO2) did not change and cannot be implicated in the fall of O2 transport. E (the ratio CMRO2/O2 transport) rose by 77%. Sham exchange transfusions in six fetuses showed that the exchange transfusion procedure itself was not responsible for this alteration. To determine whether the fall in O2 transport and the rise in E was reproducible over a range of arterial O2 contents, a third group of six fetuses was studied. Fetal arterial O2 content varied from 4 to 12 vol%, first at P50 = 17 +/- 1.8 mmHg and again after exchange transfusion at P50 = 29.6 +/- 3.9 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of membrane phospholipids in myocardial injury induced by ischemia and reperfusion
Authors: Das D. K. , Engelman R. M. , Rousou J. A. , Breyer R. H. , Otani H. , Lemeshow S.
Published: December 2017

Depletion of membrane phospholipids is known to be associated with myocardial ischemia, but its relationship to the injury involved with the reperfusion of ischemic myocardium is not known. The present study was designed to relate phospholipid degradation with reperfusion injury. The isolated in situ pig heart was subjected to 60 min of regional ischemia induced by occluding the left anterior descending (LAD) coronary artery and 60 min of global ischemia by hypothermic cardioplegic arrest followed by 60 min of reperfusion. The pigs were divided into two groups. In the treatment group, the heart was preperfused with mepacrine (0.05 mM), a known phospholipase inhibitor, for 15 min prior to LAD occlusion. In the control group, the total phospholipid content was not significantly decreased during LAD occlusion and arrest, but was reduced appreciably after reperfusion. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol followed a similar pattern. The lowering of these phospholipids during reperfusion was accompanied by enhancement of lysophosphatidylcholine. Mepacrine restored the normal levels of these phospholipids. During reperfusion, fatty acyl CoA synthetase, lysophospholipase, and lysophosphatidylcholine acyltransferase were depressed, whereas phospholipase A2 was enhanced. Mepacrine inhibited phospholipase A2, but had no effects on the other enzymes. Mepacrine also provided significant protection against reperfusion injury, as documented by the preservation of high-energy phosphate compounds and inhibition of the appearance of creatine kinase activity in the perfusate. These results suggest that membrane phospholipids play an important role in myocardial injury associated with ischemia and reperfusion, primarily because the deacylation-reacylation cycle of phospholipid biosynthesis becomes defective.
Relative flow of blood cells, platelets, and microspheres in outer and inner renal cortex
Authors: Ofjord E. S. , Clausen G.
Published: December 2017

Blood platelets (Pl) may attain a relatively high marginal concentration in arterioles, perhaps also in arteries. Along a renal interlobular artery, blood passes several successive arterioles, each arteriole receiving a small flow fraction from a narrow zone adjacent to the artery wall. Thus, in theory, the Pl concentration should cumulatively decrease as the blood approaches the outer cortex, contrary to the concentration of red and white blood cells (RBC and WBC). This was tested by assessing the concentrations of these blood elements, and for comparison, the concentrations of 0.3-, 1.8- and 3.5-micron microspheres (MS), in serial blood samples from veins separately draining the outer and inner cortex in cat kidney. The outer-to-inner cortical concentration ratio was 1.28 for WBC, 1.04 for RBC, and 0.75 for Pl, confirming the working hypothesis. The RBC demargination corresponded to that of MS smaller than 1.8 micron, the demargination of WBC to that of MS larger than 3.5 micron. In contrast to Pl the even smaller 0.3-micron MS were not marginated. Thus, the margination of platelets may not be due merely to their small size.
Succinyl trialanine p-nitroanilide hydrolytic activity in blood vessels of the rat
Authors: Ito H. , Kwan C. Y. , Daniel E. E.
Published: December 2017

Succinyl trialanine p-nitroanilide [Suc-(Ala)3-pNA] hydrolytic activity, an enzymatic activity related to elastase, in vascular wall was detected and partially characterized. Subcellular distribution of this activity closely paralleled that of plasma membrane marker enzymes, 5'-nucleotidase, and phosphodiesterase I, suggesting its association with the vascular muscle plasma membranes. The same distribution of elastolytic activity was observed. Hydrolytic activity toward Suc-(Ala)3-pNA was inhibited by EDTA, ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid but not by trypsin inhibitor. Enzyme activities were different not only between aortic muscle extracts from young and mature rats, but also among the extracts from elastic and muscular arteries, specific activity being higher in the aortas of young animals or in elastic arteries, respectively. The activity studied [Suc-(Ala)3-pNAase] in vascular wall may play a role in vascular connective tissue metabolism as well as function.