bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpha 1- and alpha 2-adrenoceptor stimulation: changes in venous capacitance in intact dogs
Authors: Appleton C. P. , Lee R. W. , Martin G. V. , Olajos M. , Goldman S.
Published: December 2017

The peripheral circulatory effects of alpha 1-adrenoceptor stimulation with methoxamine hydrochloride were compared with those of alpha 2-stimulation with UK 14304-18 in 12 intact dogs. Doses of each agent were infused to increase systemic vascular resistance and arterial pressure 50 and then 100% above control. Heart rate was controlled with atropine. At the higher dose, methoxamine increased mean aortic pressure (PAo) from a control of 77.3 +/- 1.6 to 152.9 +/- 3.2 mmHg, mean circulatory filling pressure (MCFP) from 8.0 +/- 0.4 to 13.3 +/- 1.3 mmHg, and central blood volume (CBV) from 21.3 +/- 1.1 to 25.9 +/- 1.5 ml X kg-1, whereas cardiac output did not change. UK 14304-18 increased PAo from 78.1 +/- 2.6 to 148.9 +/- 2.7 mmHg, MCFP from 7.9 +/- 0.4 to 10.6 +/- 0.4 mmHg, and CBV from 21.0 +/- 1.1 to 24.1 +/- 1.5 ml X kg-1, whereas cardiac output decreased from 151.7 +/- 9.4 to 126.3 +/- 5.8 ml X kg-1 X min-1. Mean circulatory filling pressure and CBV were higher with methoxamine than with UK 14304-18. Effective vascular compliance, determined by serial measurements of MCFP during ganglionic blockade after rapid changes in blood volume, decreased from a control value of 1.9 +/- 0.1 to 1.3 +/- 0.3 ml X mmHg-1 X kg-1 with methoxamine, but did not change with UK 14304-18 (1.9 +/- 0.1 ml X mmHg-1 X kg-1). At any given change in blood volume, there was a higher MCFP with alpha 1-stimulation compared with alpha 2-stimulation. Both agents decreased unstressed vascular volume.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell flow path influences transit time through striated muscle capillaries
Authors: Sarelius I. H.
Published: December 2017

Indirect estimates of erythrocyte transit time across capillary beds incorporate two assumptions, that the anatomically defined capillary length correctly describes the functional flow path taken by cells across the network, and that the distribution of perfused flow path lengths does not change during hyperemia. Direct measurements of cell flow paths through capillary networks, cell transit times, and associated blood flow variables, have been made using fluorescent erythrocytes as tracers of the total cell population. Observations were made in cremaster muscles from juvenile or adult anesthetized golden hamsters; these tissues have capillary networks of differing degrees of branching. In the juvenile (more branching) networks, mean functional flow path (Lf) was 351 +/- 6 (SE) micron, about twice the average distance from terminal arteriole to collecting venule (172 +/- 37 microns). In the less branching adult networks, Lf = 438 +/- 9 microns compared with the anatomically defined distance of 372 +/- 33 microns. In both groups, Lf distribution was unchanged during hyperemia produced by 10(-4) M adenosine. Directly measured cell transit times across the networks were longer than expected from previous indirect estimates: means were 3.2 +/- 0.1 s in juveniles and 4.2 +/- 0.2 s in adults, with decreases to 2.2 +/- 0.1 and 2.3 +/- 0.1 s, respectively, in hyperemia.
Prolonged responsiveness to ouabain in hypertrophied rat heart: physiological and biochemical evidence
Authors: Lelievre L. G. , Maixent J. M. , Lorente P. , Mouas C. , Charlemagne D. , Swynghedauw B.
Published: December 2017

The inotropic effect of ouabain on cardiac hypertrophy was evaluated on an isolated Langendorff rat heart preparation with performances registrated by means of an intraventricular balloon. These effects were compared with the drug action on the sarcolemma-bound Na+-K+-ATPase activity. On both normal and pressure-overload induced hypertrophied rat hearts (ventricular wt-to-body wt ratios of 2.1 and 3.3, respectively) the inotropic effect of ouabain (10(-9)-10(-4) M) was evaluated at 0.25 mM external Ca2+. Compared with normal hearts, the recovery of a normal contractile function after the inotropic response was significantly slower in hypertrophied hearts. This was valid with the two protocols applied. During a 30-min washout period, the inotropic response remained nearly unchanged in hypertrophied hearts, whereas it was almost completely reversed in control groups. Sarcolemmal vesicles from both heart groups exhibited high Na+-K+-ATPase activities (sp. act.: 105 +/- 16 mumol X h-1 X mg-1). In both normal and hypertrophied cardiac sarcolemmal preparations, the Na+-K+-ATPase was heterogeneous, with high- and low-sensitivity forms. Their relative proportion was two-to-one. In both heart groups, their respective apparent affinities for ouabain were similar (inhibitory concentration of 50% = 10(-8) and 10(-6) M, respectively). The release of ouabain from these two sites was measured, in washout experiments, by the rates of enzyme relief from inhibition. High- and low-sensitivity forms in hypertrophied heart preparations released ouabain at seven- and threefold lower rates, respectively, than the corresponding forms present in normal cardiac sarcolemmal vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac myocyte stiffness following extraction with detergent and high salt solutions
Authors: Brady A. J. , Farnsworth S. P.
Published: December 2017

Myocytes were prepared from enzymatically digested adult rat hearts and attached to concentric double-barreled suction micropipettes. Myocyte stiffness was calculated as the ratio of the oscillatory tension-to-strain amplitude, where the strain was produced by an applied 5-Hz perturbation. Stiffness, as a function of cell length, was measured in relaxing solution (pCa = 9) as the control solution, 0.5% Triton X-100 detergent, 0.47 M KCl, and 0.6 M KI. Ultrastructure of unattached cells in each solution is illustrated with electron micrographs. The dependence of cell stiffness on cell length was described by an exponential relation with a length constant that increased slightly in detergent, whereas the stiffness at control length appeared to fall. The major fall in absolute stiffness occurred with myosin extraction in KCl. Both the stiffness at control length and the slope of the ln stiffness-to-length relation declined with the disappearance of the A band. A further, but smaller, decline of stiffness occurred with KI extraction of the thin filaments. A highly compliant "ghost" remained after KI extraction but the stiffness-to-length relation was still measurable. The fall in stiffness with myosin extraction is discussed in relation to cytoskeletal filaments (titin, nebulin, and intermediate filaments.
Interactions among reflex compensatory systems for posthemorrhage hypotension
Authors: Hosomi H. , Katsuda S. , Morita H. , Nishida Y. , Koyama S.
Published: December 2017

The open-loop gains of the carotid sinus, aortic, and cardiopulmonary baroreflex systems defined as the ratio of posthemorrhage hypotension without a reflex to that with the reflex were estimated from experiments with a mild and quick hemorrhage (2 ml/kg body wt in 1-2 s) in 81 pentobarbital-anesthetized rabbits. The overall gain when all the nerves were intact was 7.4. After the carotid sinus nerves were sectioned the gain decreased to 3.0. After aortic nerve sectioning, the gain was 2.8, whereas vagotomy decreased it to 3.8. When both the carotid sinus and aortic nerves were cut, the gain was 0.9. When the aortic and vagus nerves were severed, it was 1.8. When the vagus and carotid sinus nerves were cut, it was 1.6. From these gain values the gain of the interacting component between the carotid sinus and aortic reflexes was calculated as 0.4; that between the aortic and cardiopulmonary reflexes was 0.5; and that between the cardiopulmonary and carotid sinus reflexes as 0.1. The gain of the interaction among all of these baroreflex systems was estimated to be 2.1. The results suggest that all these facilitatory interacting components play an important role in restoration of arterial pressure decrease caused by mild hemorrhage.
Methylene blue and ETYA block flow-dependent dilation in canine femoral artery
Authors: Kaiser L. , Hull S. S. , Sparks H. V.
Published: December 2017

Flow-dependent dilation of the canine femoral artery is endothelial cell dependent and is not mediated by prostaglandins, adrenergic or cholinergic receptors, an ascending message from the microcirculation, or by myogenic mechanisms. We investigated the mechanism of flow dilation in 38 pentobarbital anesthetized dogs. A femoral artery-jugular vein shunt was constructed, and femoral artery diameter was continuously measured (sonomicrometer crystals) during control and maximum flow (1 l/min). Inhibition of prostaglandin formation by indomethacin did not alter the dilation response to increased flow, but the lipoxygenase-cyclooxygenase inhibitor 5, 8, 11, 14 eicosatetraynoic acid (ETYA) irreversibly inhibited the dilation response to increased flow. The guanylate cyclase inhibitor, methylene blue, caused a dose-dependent decrease in the dilation response to increased flow. Pretreatment with the H1 receptor antagonist tripelennamine sensitized the vessel to the inhibitory effects of methylene blue. Both methylene blue and ETYA shifted the ED50 for acetylcholine relaxation two orders of magnitude to the right, but did not alter the ability of the vessel to dilate or constrict to other stimuli. These data suggest that both cyclic GMP and a non-prostaglandin metabolite of arachidonic acid are involved in flow dilation. We propose that endothelial cells release a metabolite of arachidonic acid that stimulates vascular smooth muscle guanylate cyclase leading to relaxation. The role of histamine in this system is unknown.
Ambulatory pulmonary arterial pressures in humans: relationship to arterial pressure and hormones
Authors: Richards A. M. , Ikram H. , Nicholls M. G. , Espiner E. A. , Hamilton E. J. , Richards R. D.
Published: December 2017

Six healthy volunteers were studied by use of a continuous ambulatory recording technique to document the normal range and variability of pulmonary artery pressure (PAP) and to examine its relationship to systemic arterial pressure (SAP) both at rest and during standardized interventions. Vasoactive hormone levels were measured at frequent intervals. Over 8-10 h of study the mean PAP was 15.7/6.3 mmHg. Parallel changes in PAP and SAP were observed at rest and during exercise and eating. On the contrary, PAP rose and SAP fell with hypoxia, whereas smoking was associated with a rise in SAP but no change in PAP. Sympathetic nervous system activity, as gauged by plasma norepinephrine levels, may have contributed to pressure and heart rate changes during exercise and smoking, but activity of the renin-angiotensin system was not altered by any of the maneuvers. These results provide base-line information on the level of PAP and its variability in healthy volunteers under standardized conditions. Pressures within the systemic and pulmonary circuits change in parallel under some circumstances but move in opposite directions under other conditions.
Characterization of vasopressin receptors of rat urinary bladder and spleen
Authors: Thibonnier M. , Snajdar R. M. , Rapp J. P.
Published: December 2017

By use of tritiated arginine-8-vasopressin (AVP), vasopressin specific binding sites were detected on Sprague-Dawley rat urinary bladder and spleen. In both tissues, one class of high-affinity binding sites was characterized with an equilibrium dissociation constant of 1.61 +/- 0.22 and 1.91 +/- 0.16 nM and a maximal binding capacity of 155 +/- 5 and 110 +/- 11 fmol/mg of protein, for bladder and spleen, respectively. In both tissues, several experimental arguments suggest that these receptors belong to the V1-vascular type: Highly significant correlations were found between the relative agonistic vasopressor activities of eight AVP agonists and their relative abilities to inhibit [3H]AVP binding to the receptors, whereas no such relationship existed when antidiuretic activities were considered. The same profile was also observed with the antagonistic activities of five AVP antagonists. Moreover, AVP (10(-12)-10(-5) M) did not modify the basal cyclic AMP production in either tissue. As cyclic AMP is known to respond to V2 stimulation, the data suggest that the receptors measured are the V1 type. In Dahl rats the receptor characteristics were modulated by salt diet. More interestingly, the number of spleen vasopressin binding sites was always lower in Dahl salt-resistant animals than in the Dahl salt-sensitive animals receiving either a sodium deficient or a 1% NaCl or an 8% NaCl-containing diet. The exploration of vasopressin receptors regulation should facilitate the comprehension of the role played by AVP in different models of experimental hypertension.
Contribution of prostaglandins to reperfusion-induced ventricular failure in isolated rat hearts
Authors: Karmazyn M.
Published: December 2017

This study was carried out to investigate the possible contribution of endogenous prostaglandin (PG) production to failure of contractile recovery following reperfusion of hypoperfused isolated rat hearts. A 90% reduction in coronary flow rate for 60 min resulted in a time-dependent depression of contractile force and an elevation in resting tension. Reperfusion produced a slight (approximately 11%) recovery of contractile force, whereas resting tension remained elevated. Reperfusion was a potent stimulus for PG (as assessed by 6 keto-PGF1 alpha) release and resulted in levels that were significantly higher than those observed prior to ischemia. When PG synthesis was inhibited by the nonsteroidal anti-inflammatory drugs ibuprofen, indomethacin, or acetylsalicylic acid (ASA), recovery of ventricular contractility on reperfusion was significantly higher than that seen in the absence of drugs. Ibuprofen was the most effective, producing an average recovery of 70% (P less than 0.05 from control). Indomethacin and ASA produced approximately a 40% (P less than 0.05) and 35% (P less than 0.05) recovery of contractile force, respectively. The improved recovery in contractility was significantly depressed by the addition of low concentrations of prostacyclin (PGI2) and PGF2 alpha, whereas PGE2 and 6 keto-PGF1 alpha, the hydrolysis product of PGI2, were ineffective. The effects on resting tension were inconsistent. PG release during reperfusion was unrelated either to the length of the initial period of reduced coronary flow or the degree of contractile recovery; it was attenuated either by a reduction in or by an elevation of Ca concentration. These results indicate that endogenous PGs mediate, at least in part, reperfusion-associated failure of ventricular function.
Median preoptic nucleus ablation does not affect angiotensin II-induced hypertension
Authors: Fink G. D. , Bruner C. A. , Mangiapane M. L.
Published: December 2017

Previous studies implicated the ventral median preoptic nucleus (MNPOv) in cardiovascular responses to circulating and intracerebroventricular angiotensin II (ANG II) and in normal cardiovascular and fluid homoeostasis. In the present experiments, chronically catheterized rats received continuous (24 h/day) intravenous infusions of ANG II (10 ng/min) for 5 days, and changes in mean arterial pressure, heart rate, water intake and urinary electrolyte and water excretion were determined daily. Three groups of rats were compared as follows: 1) sham-operated control rats (n = 12), 2) rats with 20-70% of the MNPOv ablated electrolytically (n = 6), and 3) rats with over 90% of the MNPOv ablated (n = 5). The organum vasculosum of the lamina terminalis was intact in all three groups. Base-line values of all measured variables were identical in the three groups on two control days preceding ANG II infusion and on two recovery days after infusion. During the administration of ANG II for 5 days, mean arterial pressure rose significantly (and similarly) in all three groups of rats; no other variable was significantly affected by ANG II infusion. These results suggest that neural pathways originating in, or passing through, the MNPOv region are not critical in the pathogenesis of ANG II-induced hypertension in the rat.
Vascular capacitance responses to hypercapnia of the vascularly isolated head
Authors: Gaddis M. L. , MacAnespie C. L. , Rothe C. F.
Published: December 2017

Hypercapnic stimulation of the brain may account for some of the decrease in vascular capacitance (venoconstriction) seen with whole-body hypercapnia. Six mongrel dogs were anesthetized with alpha-chloralose and paralyzed with pancuronium bromide. The vagi were cut and the carotid bodies and sinuses were denervated. The head circulation was isolated and perfused with normoxic [arterial partial pressure of O2 (Pao2) = 112 mmHg], normocapnic (PaCO2 = 40 mmHg) blood, or one of three levels of normoxic, hypercapnic (PaCO2 = 56, 68, or 84 mmHg) blood. A membrane oxygenator was used to change gas tensions in the perfusate blood. The systemic circulation received normoxic, normocapnic blood (Pao2 = 107 mmHg; PaCO2 = 32 mmHg). Systemic arterial pressure increased from 111 to 134 mmHg, and heart rate decreased from 174 to 150 beats/min with a head blood PaCO2 of 84 mmHg. Central blood volume was not affected by head hypercapnia. Cardiac output significantly decreased only with a head blood PaCO2 of 84 mmHg. Mean circulatory filling pressure increased by 0.014 mmHg/1 mmHg increase in head PaCO2. The sensitivity of the total peripheral resistance to cephalic blood hypercapnia was 0.88%/mmHg, whereas that for the mean circulatory filling pressure was only 0.19%/mmHg. We conclude that stimulation of the brain, via perfusion of the head with hypercapnic blood, causes a small but significant increase in mean circulatory filling pressure, due to systemic venoconstriction.
Angiotensin receptors and pressor hyperresponsiveness in renal prehypertensive rabbits
Authors: Zeigler D. W. , Johnson J. A. , Koivunen D. G. , Siripaisarnpipat S. , Fowler W. L. , Dostal D. E. , Payne C. G.
Published: December 2017

This study consisted of five different experiments with conscious rabbits. In experiment 1, the angiotensin II (ANG II) antagonist [Sar1-Ala8]ANG II infused iv into one-kidney rabbits with renal artery stenosis (RAS) of 3 days' duration, at a dose that blocked pressor responses to ANG II, did not decrease the exaggerated pressor responses to norepinephrine (NE). In experiment 2, captopril infused iv into one-kidney, 3-day, RAS rabbits blocked pressor hyperresponsiveness to NE, and the concurrent infusion of [Sar1-Ala8]ANG II did not reestablish pressor hyperresponsiveness, indicating that this ANG II analogue had no agonistic action to promote hyperresponsiveness to NE. In experiment 3, infusion of ANG II at a subpressor dose (6.7 pmol . min-1 . kg body wt-1) into normal rabbits resulted in pressor hyperresponsiveness to NE, which was blocked by [Sar1-Ala8]ANG II. Experiment 4 involved infusing [Sar1-Ala8]ANG II or [Sar1-Ile8]ANG II at various doses into 3-day RAS rabbits, to determine their abilities to attenuate the pressor responses to ANG II (100 ng/kg) and the pressor hyper-responses to NE (800 ng . min-1 . kg-1). [Sar1-Ile8]ANG II decreased the ANG II pressor responses at an ID50 dose of 64 +/- 5 (SEM) pmol . min-1 . kg-1 and attenuated the NE pressor hyper-response at an ID50 dose of 65 +/- 5 pmol . min-1 . kg-1; [Sar1-Ala8]ANG II diminished the ANG II pressor response at an ID50 dose of 757 +/- 247 and the NE pressor hyper-response at an ID50 dose of 10,061 +/- 944 pmol . min-1 . kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
A method for measurement of internal longitudinal resistance in papillary muscle
Authors: Buchanan J. W. , Oshita S. , Fujino T. , Gettes L. S.
Published: December 2017

We have modified the original Weidmann method for the measurement of internal longitudinal resistance in ventricular muscle by using air rather than silicon oil to insulate guinea pig papillary muscles and by omitting the tetrodotoxin inactivation of a portion of the preparation and have examined the requirements necessary for the theoretical assumptions to be satisfied by this or similar preparations. We found a homogeneous depolarization wavefront beyond about 1 mm from the stimulating electrodes. The adequacy of the interelectrode spacing was identified by a discrete plateau in the extracellular potential recording. The extracellular resistance in this preparation was sensitive to changes in the volume of the extracellular compartment, which we manipulated by changing inflow and outflow rates, and to changes in total ionic content of the superfusate. Our results establish the essential nature of maintaining constant flow rates and total ionic content and suggest that changes in volume and ionic content of a restricted extracellular space could conceivably influence conduction in vivo.
Sympathomimetic pressor responses to thyrotropin-releasing hormone in rats
Authors: Mattila J. , Bunag R. D.
Published: December 2017

Cardiovascular responses to centrally administered thyrotropin-releasing hormone (TRH) were studied in urethan-anesthetized rats to allow continuous recording of attendant changes in sympathetic nerve activity. Intracerebroventricular infusions of TRH (0.05-5.0 micrograms) consistently increased not only blood pressure and heart rate, but also spike frequency in splanchnic, renal, or cervical sympathetic nerves. Parasympathetic inhibition seemed unlikely because TRH responses were unaltered by cholinergic blockade with atropine, and efferent vagal nerve firing, instead of being reduced, was actually increased by TRH. An increased secretion of endogenous vasopressin also appeared unlikely, since TRH responses were essentially unaffected by either hypophysectomy or pretreatment with a vasopressin antagonist. Inasmuch as pharmacological ganglion blockade with pentolinium eliminated increases in splanchnic nerve firing but reduced the attendant tachycardia by only 50%, residual tachycardia after ganglion blockade was considered partly due to persistent sympathetic cardioaccelerator tone. On the other hand, because pressor responses to TRH were always accompanied by increased sympathetic nerve firing and were completely abolished after pentolinium-induced ganglioplegia, they were attributed solely to sympathetic hyperactivity.
Effect of vasopressin and phenylephrine on arterial pressure and heart rate in conscious dogs
Authors: Robinson J. L.
Published: December 2017

The effect of arginine vasopressin (AVP) and phenylephrine (PE) infusions on mean arterial pressure (MAP) and heart rate (HR) were compared in conscious dogs with all autonomic receptors intact (I), during muscarinic blockade (MB) and during ganglionic blockade (GB). After either MB or GB, the dose-MAP response curve for AVP and PE was shifted to the left of the I response curve; a greater shift was observed with AVP than with PE. The MAP threshold after GB for AVP and PE occurred at 10 and 50% of the threshold dose observed during the I response, respectively. Not only did the MAP threshold occur at a lower dose after MB and GB, but also the slope of the response curve was steeper than that of the I response. Comparing the amount of drug necessary to increase MAP 25 mmHg above control for PE and AVP before and after GB, the intact PE response required 4.3 +/- 1.0 (P less than 0.01) times more drug than during GB versus the intact AVP required 16.8 +/- 2.8 (P less than 0.01) times more drug than during GB. The baroreflex control of HR when all receptors were intact was 3.4 +/- 0.4 (P = 0.001) times more sensitive during AVP compared with PE; no differences were observed after MB. There were no significant changes in HR to AVP or PE after GB, thus indicating a lack of a direct effect of these agents on the HR. Our results show that MB and GB equally potentiate the pressor effects of AVP and PE, and the augmentation was much greater for AVP than for PE. The difference in the potentiation of these two vasoconstrictors is consistent with the finding that the baroreflex sensitivity during AVP was enhanced compared with PE. We have postulated that, in the resting conscious dog, AVP increases the sensitivity of the baroreflex primarily by producing a greater level of parasympathetic tone to the heart in response to a given pressure stimulus.
Changes in canine cardiac function and venous return curves by the carotid baroreflex
Authors: Greene A. S. , Shoukas A. A.
Published: December 2017

Venous return curves and cardiac function relationships were simultaneously determined in 10 pentobarbital-anesthetized dogs at three different isolated carotid sinus pressures. Changing carotid sinus pressure (CSP) between 50 and 200 mmHg produced large changes in the zero flow intercept of the venous return curves from 15.37 +/- 0.97 to 11.94 +/- 1.36 mmHg (P less than 0.001) but no change in slope. These changes in the intercept of the venous return curve were due to alterations in systemic vascular capacity caused by the carotid sinus baroreceptor reflex. Changes in the cardiac function curve with baroreceptor pressure were masked by concomitant changes in arterial pressure afterload; however, when arterial pressure was controlled, there was a significant change in the slope of the cardiac function curve from 60.32 +/- 26.9 to 37.06 +/- 13.31 ml X min-1 X kg-1 X mmHg-1 as CSP was changed from 50 to 200 mmHg. We conclude that changes in vascular capacity are the primary mechanism responsible for changes in cardiac output during activation of the carotid sinus baroreflex.
Ultrastructural features of atrial peptide secretion
Authors: Page E. , Goings G. E. , Power B. , Upshaw-Earley J.
Published: December 2017

The ultrastructural bases of exocytotic extrusion of atrial peptides were reexamined in electron micrographs of thin-sectioned or freeze-fractured mouse atria. Exocytotic extrusion was demonstrated in both thin-sectioned and freeze-fractured atrial myocytes. Ultrastructural evidence suggested that the necks of plasmalemmal caveolae may constitute preformed pathways for extrusion of secretion from granules fusing with caveolae. Multiple subsarcolemmal foci with peripheral Golgi cisterns and accumulations of granules, indicating peripheral processing of secretory proteins, were striking features of mouse and rat atria, and were present but rare in sheep and dog atria. Conspicuous focal ellipsoidal deposits, a new structure, approximately 1.6-4.6 micron long and approximately 0.8-1.8 micron wide, consisting of amorphous cytoplasmic material that is penetrated peripherally by tubules connecting with secretion-containing "multivesicular bodies," were present in some mouse atrial myocytes, but were absent in myocytes of mouse ventricle and rat, dog, and sheep atria.
In vivo mechanical behavior of canine pericardium
Authors: Mann D. , Lew W. , Ban-Hayashi E. , Shabetai R. , Waldman L. , LeWinter M. M.
Published: December 2017

We examined the in vivo mechanical behavior of the pericardium by measuring simultaneous atrial and intrapericardial pressures and mutually orthogonal, circumferential, and longitudinally oriented pericardial segment lengths (ultrasonic gauges) in 10 open-chest dogs. Venous return was varied by a combination of caval occlusion followed by volume loading. Up to a mean left atrial pressure of 25 mmHg, the pericardium lengthened virtually exclusively in the circumferential direction (n = 9). Thus, at an intrapericardial pressure of 6.0 +/- 1.0 (+/- SD) mmHg, circumferential strain (normalized to length at pericardial pressure 0 mmHg) was 0.30 +/- 0.28, whereas longitudinal strain was 0.02 +/- 0.06 (P less than 0.05). In five of these dogs, alteration of external pericardial loading by severing the pericardial diaphragmatic attachments did not change the difference between circumferential and longitudinal strain, and in two the same directional strain difference was observed during production of cardia tamponade. In three additional dogs the square of the circumferential segment length was closely correlated with the directly measured intrapericardial volume when saline was infused into the pericardial space in an in situ, arrested heart preparation. Our results indicate that there is marked directional variability in lengthening of the pericardium when the volume of its contents is altered in vivo. This phenomenon is probably the result of complex interactions between the properties of the pericardial tissue and the influence of its internal and external loads.
Comparison of in situ and in vitro studies of pericardial pressure-volume relation in dogs
Authors: Freeman G. L. , Little W. C.
Published: December 2017

Whether the material properties of the pericardial membrane are the key determinants of the in situ pericardial pressure-volume relation is not known. Although both the pressure-volume relation of the intact pericardium and the stress-strain relation of isolated pericardial samples are nonlinear, it is not clear how closely these phenomena are related. To directly examine this question we compared the pressure-volume, pressure-normalized volume, and stress-strain relations of pericardia from six dogs tested both in situ and in vitro. The curves generated under the two sets of conditions were different. The transition from the compliant to the noncompliant portion of the curve was more acute under in vitro conditions. Nonlinear regression analysis using a monoexponential function of the form Y = alpha (e beta chi-1) showed beta, the proportionality constant for the slope of the curve, to be larger for each form of analysis under in vitro testing conditions as follows: 0.002 +/- 0.009 vs. 0.078 +/- 0.029, P less than 0.002 for pressure-volume; 3.52 +/- 1.75 vs. 11.03 +/- 5.31, P less than 0.005 for pressure-normalized volume; and 19.6 +/- 6.6 vs. 62.3 +/- 18.8, P less than 0.001 for stress-strain. These differences in the pressure-volume relation of the intrapericardial space in situ and the isolated pericardium in vitro suggest that pericardial attachments present in situ may buffer the loading of the membrane itself. We conclude that the pressure-volume relation of the intrapericardial space is only partly determined by the properties of the isolated pericardium alone and is also influenced by other components of the intact pericardium.
Influence of pacing site on canine left ventricular contraction
Authors: Burkhoff D. , Oikawa R. Y. , Sagawa K.
Published: December 2017

We investigated the influence of pacing site on several aspects of left ventricular (LV) performance to test the hypothesis that "effective ventricular muscle mass" is reduced with direct ventricular pacing. All studies were performed on isolated supported canine hearts that were constrained to contract isovolumically. To determine the influence of pacing site on magnitude and time course of isovolumic LV pressure (P) generation, LVP waves were recorded in eight isolated hearts paced at 130 beats/min. Pacing was epicardially from atrium, LV apex, LV free wall, right ventricular free wall (RVF), and endocardially from right ventricular endocardium. In a given heart, peak LVP was greatest with atrial pacing and smallest with RVF pacing, the difference being on average 26 +/- 10% (mean +/- SD) of the former pressure. The other pacing sites produced intermediate peak LVPs. When instantaneous LVP waves, obtained while pacing from each of the five sites, were normalized by their respective amplitudes, they were virtually superimposable up to the time of peak pressure and only slightly different during the remainder of the cardiac cycle. With changes in pacing site there was a linear negative correlation (r = 0.971) between changes in peak pressure and changes in duration of the QRS complex of a bipolar epicardial electrogram with an average slope of -0.51 mmHg/ms. Compared with atrial pacing, the slope of the end-systolic pressure-volume relation, Ees, was decreased with ventricular pacing, but Vo, the volume axis intercept, was relatively constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Tetraethylammonium-induced phasic arterial constriction: temporal and spatial characteristics
Authors: Lambert C. R. , Pepine C. J.
Published: December 2017

In vitro techniques were developed to characterize temporal, spatial, and mechanical characteristics of tetraethylammonium (TEA)-induced phasic contractile activity in pressurized perfused canine femoral artery segments. Power spectral analysis revealed TEA-induced phasic activity to be included in the bandwidth from 0.004 to 0.016 Hz. The level of intraluminal pressure did not influence frequency characteristics of this activity. Mean total tangential stress increased proportionately with intraluminal pressure, whereas both mean developed tangential stress and the strain index mean percent change of external diameter showed a plateau in the 80- to 120-mmHg pressure range. TEA-induced phasic activity propagated longitudinally in all arteries studied. The velocity of longitudinal propagation (V, cm/s) varied with intraluminal pressure in a nonlinear fashion with V = 0.79 +/- 0.05 at 40 mmHg, V = 0.72 +/- 0.05 at 80 mm Hg, and V = 0.85 +/- 0.05 at 120 mmHg. V was not affected by tetrodotoxin, and phasic activity was abolished by verapamil. Phasic activity showed a primary direction of propagation 81 +/- 7% of the time; however, this direction was variable in all arteries. Thus vascular smooth muscle activation by TEA, which has been proposed as a model for coronary artery spasm, produces propagated constrictor responses in the ultra-low-frequency band with pressure-sensitive velocity characteristics and mechanical properties that are optimized in the physiological pressure range.
A new technique for the study of vascular presynaptic receptors in freely moving rats
Authors: Remie R. , Zaagsma J.
Published: December 2017

A technique is described in which a silicon catheter is utilized for permanent catheterization of the portal vein, and curved platinum stimulation electrodes around this vein are used for the stimulation of the local nervous plexus. The method has a success ratio of over 70% during a period of more than 2 mo. Five animals were used in experiments over a period longer than 5 mo. Using this technique, we investigated the influence of variation of current density, pulse duration, and frequency of stimulation on the electrically evoked release of norepinephrine in portal blood. Enhancement of all stimulation parameters proportionally increased the evoked norepinephrine release. The alpha 2-adrenoceptor antagonist yohimbine was found to increase basal norepinephrine levels 4.43-fold and facilitated the evoked release additionally with a factor of 4.70. The results show that noradrenergic neurotransmission in the portal vein nervous plexus is controlled presynaptically by a strong local alpha 2-adrenergic autoinhibition. The method offers the means to explore locally the presynaptic modulation of endogenous neurotransmitter release in unrestrained unanesthetized animals.
Voltage-dependent action of tetrodotoxin in mammalian cardiac myocytes
Authors: Vassilev P. M. , Hadley R. W. , Lee K. S. , Hume J. R.
Published: December 2017

Single Na+ channel currents have been examined in isolated guinea pig ventricular myocytes using the patch-clamp technique. The effects of lidocaine, extracellular calcium [(Ca)o], and tetrodotoxin on patch Na+ channel availability were assessed using ensemble averages of Na+-channel openings during depolarizing test potential steps from 7 to 10 different patch-holding potentials in each cell-attached patch. In six control patches, the potential for 50% channel availability (Vh) was -15 mV (relative to an average resting membrane potential of -80 mV). Exposure of patches to either lidocaine or elevated (Ca)o produced the expected shifts in Vh [average -22 mV for lidocaine and +10 mV for 6 mM (Ca)o]. Exposure of patches to tetrodotoxin (0.5 microM or 1.0 microM) produced a dose-dependent hyperpolarizing shift of Vh (average -10 and -17 mV) compared with control patches. The hyperpolarizing shift by tetrodotoxin was observed with pulses applied at frequencies of 1.0 or 0.067 Hz. In agreement with earlier maximal upstroke velocity studies in the same preparation, we conclude that block of ventricular Na+ channels by tetrodotoxin exhibits genuine steady-state voltage dependence.
Effects of 2-tetradecylglycidic acid on myocardial function in swine hearts
Authors: Miller W. P. , Liedtke A. J. , Nellis S. H.
Published: December 2017

Fatty acids in excess impair myocardial function in intact hearts both during aerobic and ischemic blood flow. The purpose of these studies was to determine whether decreases in acylcarnitine, effected by 2-tetradecylglycidic acid (TDGA), would result in the preservation of myocardial function in intact hearts during fatty acid excess. Two groups of intact working swine hearts in which serum fatty acids were augmented three- to fourfold were perfused extracorporeally with whole blood and compared over 90 min. Labeled [U-14C]palmitate was administered selectively into the left anterior descending coronary circulation to follow fatty acid oxidation, and regional myocardial function was assessed with ultrasonic crystals. Coronary flow in this bed was decreased by 50% over the final 30 min of perfusion. Treated swine (n = 10) were compared with a placebo-treated control group (n = 9). At similar levels of aerobic flow, TDGA effected a marked decrease in 14CO2 production during 60 min of aerobic perfusion, but levels were similar during the final 30 min of ischemia. Tissue levels of acylcarnitine were significantly reduced and acetyl-CoA levels significantly increased in TDGA-treated hearts both in aerobic and ischemic myocardium. This inhibition of fatty acid metabolism during aerobic flow was associated with an increase in regional myocardial shortening in the treated group. This occurred at similar levels of O2 consumption, evidencing enhanced carbohydrate substrate utilization. During the first 30 min of ischemia 14CO2 production and mechanical function were compromised similarly, whereas lactate production was 70% less (P less than 0.025) in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac function in spontaneously hypertensive diabetic rats
Authors: Rodrigues B. , McNeill J. H.
Published: December 2017

The isolated perfused working heart was used to study hypertensive diabetes-induced alterations in cardiac function at 6 and 12 wk after diabetes was induced. At 6 wk after diabetes induction, cardiac performance was depressed in the diabetic animals. However, there was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-wk study. Hearts from 12-wk SHR and Wistar diabetic animals exhibited a depressed left ventricular developed pressure and positive and negative dP/dt when compared with control animals. However, this depression was not seen in the WKY diabetic animals. In addition, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and were unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats as seen in the other two diabetic groups. This normal lipid metabolism and thyroid status could, in part, explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than with either disease alone and is associated with a significant mortality.
Systemic and regional hemodynamic effects of leukotrienes D4 and E4 in the conscious rat
Authors: Eimerl J. , Siren A. L. , Feuerstein G.
Published: December 2017

The effect of leukotrienes (LTs) D4 and E4 on systemic and regional hemodynamic variables were studied in the conscious rat (n = 5-9). Renal (R), mesenteric (M), and hindquarter (HQ) blood flow (BF) were monitored by directional pulsed Doppler velocimetry, and mean arterial blood pressure (MAP) and heart rate were recorded through a catheter in the femoral artery. In a separate series of experiments, cardiac index (CI) was measured by the thermodilution method. Systemic injection of LTD4 or LTE4 (0.1-10 micrograms/kg) produced dose-dependent pressor responses; BF in the M, HQ, and R vessels declined, due to increased vascular resistance (VR) at the following order: M much greater than HQ greater than R. Low doses of LTD4 or LTE4 produced vasodilation in the HQ area. Infusion of LTD4 (3 micrograms X kg-1 X min-1) for 10 min produced progressive and pronounced vascular constriction in the M and HQ regions along with reduction in BF. The LTD4 infusion also markedly decreased CI with a concomitant rise in total peripheral resistance index (TPRI). Indomethacin (5 mg/kg iv) pretreatment did not modify any of the hemodynamic effects of LTD4 or LTE4. FPL 55712 (10 mg/kg iv) and LY 171883 (30 mg/kg iv), two different LT-receptor antagonists, partially blocked the constriction effects of these LTs. LY 171883, but not FPL 55172, blocked the HQ vasodilation produced by LTE4. LY 171883 alone increased HQ-BF and reduced HQ-VR. These data indicate that LTD4 and LTE4 are potent constrictors of the M vascular bed, but at low doses they also produce dilation of the HQ blood vessels. Furthermore, no escape from the effects of prolonged infusion of the LTs was demonstrated in this species. Finally, the hemodynamic responses to LTD4 and LTE4 in the conscious rat are independent of cyclooxygenase products of LTs and are only partially blocked by FPL 55712 or LY 171883. These studies taken together suggest a differential distribution of multiple LT receptors in the rat vasculature.
Suppressive effect of acetylcholine on action potentials of canine paranodal fibers
Authors: Tse W. W.
Published: December 2017

The canine atrioventricular (AV) junction comprises three major tissues: paranodal fibers (PNF), AV node (AVN), and His bundle (HB). In the present study, dissection-exposed, in vitro canine AV junctional preparations were used. The object of the study was to determine whether the PNF or AVN was more sensitive to the suppressive effect of acetylcholine (ACh). In five experiments these tissues were stimulated antegradely and retrogradely, and their action potentials were recorded simultaneously under the influence of ACh (0.5 micrograms/ml). Results indicated the PNF were more sensitive to the suppressive effect of ACh than were the AVN. In another group of 13 experiments, the effects of ACh at 0.05-0.3 micrograms/ml on rate of rise of phase 0 of action potentials (Vmax), peak potential, resting membrane potential, and action potential duration of the PNF were determined. Results indicated that ACh exerted a strong suppressive effect on Vmax and amplitude of the action potentials and had little effect on the resting membrane potential and action potential duration of the PNF. In 10 of 13 preparations, ACh also suppressed the response of PNF, resulting in generation of one action potential to every two stimuli. In conclusion, these findings suggest that PNF could be the tissue responsible for vagal-induced AV conduction block.
Fetal blood volume, vascular pressure, and heart rate responses to fetal and maternal hyperosmolality
Authors: Woods L. L. , Brace R. A.
Published: December 2017

Our purpose was to explore the fetal cardiovascular responses to osmotic hydration or dehydration of the fetus. Chronically catheterized pregnant sheep with a single fetus, averaging 130 days gestation (term, 145-150 days), were studied. After an intravenous injection of 20 ml of 9% NaCl into the fetus (n = 6), fetal osmolality increased by a peak of 20 +/- 2 (SE) mosmol/kg and returned to control in 1.5-2 h. Fetal blood volume, mean arterial pressure, venous pressure, and heart rate increased by 17 +/- 4 ml, 5 +/- 1 mmHg, 3 +/- 1 mmHg, and 19 +/- 6 beats/min, respectively, at 2 min postinjection. These variables returned to normal within 20-60 min. After an intravenous injection of 240-300 ml of 9% NaCl into the ewe (n = 7), maternal osmolality increased by a peak of 48 +/- 4 mosmol/kg; fetal blood volume decreased by 36 +/- 6 ml, fetal vascular pressures were unchanged, and fetal heart rate decreased by 43 +/- 9 beats/min at 15 min postinjection. Fetal blood volume and heart rate returned to normal within 1 h even though fetal and maternal osmolalities were elevated by 20-25 mosmol/kg. With transplacental fluid movements in opposite directions following the fetal versus maternal hypertonic injections, these studies show that fetal blood volume is well regulated following osmotic hydration or dehydration, except for short-term transients lasting less than or equal to 1 h. Although fetal vascular pressures increased in parallel with blood volume following osmotic hydration, their lack of change following osmotic dehydration suggests a constriction of the fetal vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of reduced oxyhemoglobin affinity on cerebrovascular response to hypoxic hypoxia
Authors: Koehler R. C. , Traystman R. J. , Jones M. D.
Published: December 2017

Increasing P50 (PO2 at 50% oxyhemoglobin saturation) reduces cerebral blood flow (CBF) during arterial normoxia. We tested the hypothesis that increasing P50 also diminishes the CBF response to isocapnic hypoxic hypoxia and that it reduces the response in proportion to the reduced normoxic CBF. P50 was increased in nine unanesthetized newborn lambs from 26.3 +/- 1.7 (+/-SE) to 36.6 +/- 2.0 Torr by isovolemic exchange transfusion with low-affinity, adult sheep blood. Microsphere-determined CBF was decreased 22% during arterial normoxia. The slope of the response curve to reduced arterial O2 content (CaO2) was proportionately attenuated by 26% with no change in O2 uptake. Consequently, O2 transport (CBF X CaO2) was reduced by a constant amount at each CaO2 level. The percentage decrease in CBF at the higher P50 was thus independent of CaO2, and the percentage increase in CBF as CaO2 fell was independent of P50: the effects of P50 and CaO2 were independent. Common to alterations in both P50 and CaO2 are alterations in capillary and tissue PO2. In this study the variable closest to capillary PO2 was sagittal sinus PO2. We found that when venous PO2 was altered by changing CaO2, the change in CBF was equivalent to that following the same alteration in venous PO2 after a change in P50. The percentage increase in venous PO2 after exchange transfusion was approximately one-half that of the increase in P50. About one-half of the potential increase in cerebral venous PO2 was therefore eliminated by a compensatory reduction in cerebral O2 transport over a wide range of CaO2.
Is peak quadriceps blood flow in humans even higher during exercise with hypoxemia?
Authors: Rowell L. B. , Saltin B. , Kiens B. , Christensen N. J.
Published: December 2017

Blood flow (Q) to quadriceps muscles was measured by thermal dilution in six men during rest and dynamic exercise [20, 38, and 42.5-60 W (peak load)] restricted to quadriceps of one leg in normoxia (N) and hypoxemia (H; 10-11% O2). Without exception Q and quadriceps vascular conductance were higher in H. Arterial mean pressure, lactate, norepinephrine, and epinephrine all rose when work exceeded 20 W. Q in N was 0.25, 3.28, 4.27, and 5.81 l/min (rest to peak exercise) and in H was 0.25, 4.08, 5.24, and 6.58 l/min. Peak Q per 100 grams of muscle (quadriceps mass = 2.2 kg) was 273.3 (N) and 308.8 ml/min (H). Quadriceps VO2 (Q X femoral A-VO2 difference) was 25, 388, 556, and 771 ml/min (N) and 25, 390, 556, and 743 (lower peak load in H)-net mechanical efficiency was 23%. Muscle O2 delivery (Q X arterial O2 content) was unaffected by H; O2 extraction fell in H but femoral venous O2 content remained near 6 (N) and 5 ml/100 ml (H) at all workloads, in contrast to much lower values in whole body exercise. In H muscle Q can rise to even higher peak values, without apparent limit, when the mass of active muscle is too small to overwhelm the pumping capacity of the heart.