bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans
Authors: Delgado-Aros Silvia , Kim Doe-Young , Burton Duane D. , Thomforde George M. , Stephens Debra , Brinkmann Benjamin H. , Vella Adrian , Camilleri Michael
Published: December 2017

Glucagon-like peptide-1 (GLP-1) relaxes the stomach during fasting but decreases hunger and food consumption and retards gastric emptying. The interrelationships between volume, emptying, and postprandial symptoms in response to GLP-1 are unclear. We performed, in healthy human volunteers, a placebo-controlled study of the effects of intravenous GLP-1 on gastric volume using99mTc-single photon emission computed tomography imaging, gastric emptying of a nutrient liquid meal (Ensure) using scintigraphy, maximum tolerated volume (MTV) of Ensure, and postprandial symptoms 30 min after MTV. The role of vagal cholinergic function in the effects of GLP-1 was assessed by human pancreatic polypeptide (HPP) response to the Ensure meal. GLP-1 increased fasting and postprandial gastric volumes and retarded gastric emptying; MTV and postprandial symptoms were not different compared with controls. Effects on postprandial gastric function were associated with reduced postprandial HPP levels. GLP-1 does not induce postprandial symptoms despite significant inhibition of gastric emptying and vagal function; this may be partly explained by the increase in postprandial gastric volume.
Increased activity and expression of matrix metalloproteinase-9 in a rat model of distal colitis
Authors: Medina Carlos , Videla Sebastián , Radomski Anna , Radomski Marek W. , Antolín María , Guarner Francisco , Vilaseca Jaime , Salas Antonio , Malagelada Juan-R.
Published: December 2017

Matrix metalloproteinases may play a role in tissue remodelling and destruction associated with inflammation. We investigated activity and expression of matrix metalloproteinases in a rat model of colitis and tested the therapeutic potential of a synthetic inhibitor (CGS-27023-A). Colitis was induced by dextran sulphate sodium (at 5% in drinking water for 5 days) in a group of eight rats, whereas a matched control group received plain water. Activity and expression of matrix metalloproteinases were measured in colonic tissue homogenates using zymography and Western blot on days 3 and 5 after induction of colitis. In another set of experiments, two groups of colitic rats (20 per group) were treated with CGS-27023-A (20 mg/kg) or vehicle, respectively. On days 5 and 14, colonic mucosal lesions were blindly scored by microscopic examination. Induction of colitis led to a significant upregulation of matrix metalloproteinase-9 protein and its activity, but no change in matrix metalloproteinase-2 activity was observed. Treatment with CGS-27023-A significantly decreased the extent and severity of epithelial injury but did not influence mucosal repair. We conclude that increased activity of matrix metalloproteinases may contribute to epithelial damage in this model of colitis.
Thermally induced myocardial preservation and necrosis in deprived fetal mouse hearts
Authors: Roeske W. R. , Ingwall J. S. , DeLuca M. , Sybers H. D.
Published: December 2017

Cultured fetal mouse hearts deprived of oxygen and glucose were used to examine the effect of temperature on the mechanical, biochemical, and ultrastructural responses of the deprived myocardium to assess the utility of this in vitro model for studying myocardial necrosis, preservation, and repair. After 4 h of deprivation at 4, 24, 37, or 42 degrees C, 1) beating had ceased;2) ATP levels were decreased by 22% for 4 degrees C insults, 69% for 24 degrees C, 89% for 37 degrees C, and 97% for 42 degrees C; 3) CPK and LDH levels were unchanged; and 4) ultrastructural changes were observed. After 24 h of recovery from deprivation, 1) beating resumed, except for 42 degrees C;2) ATP levels were 102% of control for 4 degrees C; 99% for 24 degrees C; 62% for 37 degrees C; and 4% for 42 degrees C; 3) LDH content was decreased by 0% at 4 degrees C; 6% at 24 degrees C; 35% at 7 degrees C; and 70% at 42 degrees C; and 4) CPK content decreased similarly. Hypothermia protected deprived myocytes while hyperthermia accelerated cell necrosis. Combining deprivation with thermal insult in this in vitro model provides a spectrum of myocardial damage for studying the effect of interventions on repair processes and on metabolic changes in jeopardized myocardium.
Computer simulation of ischemic rat heart purine metabolism. II. Model behavior
Authors: Kohn M. C. , Garfinkel D.
Published: December 2017

The behavior of a model for the partial depletion of adenine nucleotides in the perfused rat heart has been compared for ischemic and high coronary flow anoxic conditions. The accumulation of noradrenaline in the interstitial fluid greatly activates adenylate cyclase ultimately resulting in the degradation of 11.02 micronmol/g dry wt of ATP to adenosine, inosine, and hypoxanthine in 30 min. The high coronary flow rate during anoxic perfusion promotes washout of the noradrenaline from the interstitial fluid so that the hormone accumulates to only one fifth of its highest level in ischemia. This results in only slight activation of adenylate cyclase and in insignificant degradation of ATP in 2 min. The behavior of the model has been examined for two aerobic conditions--a transition from light to heavy work (2 min) and a transition from substrate-free to glucose perfusion (12 min), In both cases adenylate cyclase was not activated above its basal activity, and insignificant depletion of adenine nucleotides is predicted by the model.
Ventral root mapping of cardiac nerves in the canine using evoked potentials
Authors: Kostreva D. R. , Zuperku E. J. , Cusick J. F. , Kampine J. P.
Published: December 2017

The sympathetic efferent contribution of left ventral roots T2, T3, and T4 to some cardiac nerves was studied using evoked potentials in mongrel dogs anesthetized with sodium pentobarbital. Electrical stimulation of the ventral roots while recording evoked potentials from the sympathetic chain, anterior ansa subclavia, posterior ansa, ventrolateral cervical cardiac nerve, ventromedial cervical cardiac nerve, and the vagosympathetic trunk demonstrated that A-, B-, and C-type fibers exist in these efferent neural pathways. The range of conduction velocities observed was 0.7-104 m/s. T2 contributed the largest number of A-type fibers, and T2 and T3 contributed C-type fibers equally, while T4 had the least number of fibers coursing through the cardiac nerves.
Development of SHR hypertension and cardiac hypertrophy during prolonged beta blockade
Authors: Pfeffer M. A. , Pfeffer J. M. , Weiss A. K. , Frohlich E. D.
Published: December 2017

Spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were treated with beta-adrenergic receptor inhibiting drugs (either propranolol or timolol) from conception until 12 weeks of age to determine if this therapy would alter the development of systemic hypertension or left ventricular hypertrophy. Therapy (propranolol or timolol, 500 mg/liter drinking water) was initiated with breeding parents and continued throughout the pregnancy, nursing, and postweaning periods. Although the heart rates of beta-adrenergic receptor inhibited WKY and SHR rats were consistently reduced with respect to their respective tap-water controls, this therapy did not alter body growth. Hemodynamic studies demonstrated reduced central venous pressure, cardiac index, and maximum acceleration of aortic flow in the beta-adrenergic inhibited rats. In spite of these findings, the arterial pressure of the treated rats and the degree of left ventricular hypertrophy of the SHR were unaltered by treatment. Thus, administration of the beta-adrenergic receptor blocking agents, propranolol or timolol, from conception through the developmental stage of SHR hypertension, failed to alter either the progressive rise in arterial pressure or the development of hypertensive vascular disease and left ventricular hypertrophy.
Effect of vasopressin on the mixing of portal venous blood in awake man
Authors: Erwald R. , Wiechel K. L. , Strandell T.
Published: December 2017

Transumbilical portal venous catheterization was performed in 11 patients for diagnostic selective portography. By use of a multiple-catheter technique, the effects of intravenous infusion of [8-lysine]vasopressin on portal venous mixing of tributary flows was measured by simultaneous blood sampling from the left and right portal branch, taking advantage of the oxygen saturation difference between splenic and superior mesenteric venous blood and also by infusion of 133Xe into one of the portal tributaries. Slight signs of incomplete portal mixing were observed at rest in eight of nine patients. During vasopressin infusion, the heterogeneity of oxygen saturation and xenon activity in the portal branches increased significantly. There was also a significant average shift of splenic venous blood toward the left portal branch with, in some patients, only splenic blood in this branch. Streamlining thus was a dynamic phenomenon related to the reduced and altered portal venous flow pattern. This must be considered during flow measurements, and might also have pathophysiological significance in liver diseases.
Transmural metabolic gradients in the normal dog left ventricle: effect of right atrial pacing
Authors: Allison T. B. , Holsinger J. W.
Published: December 2017

The effects of atrial pacing on tissue metabolite levels known to be sensitive to ischemia were examined. Anesthetized dogs were thoracotomized and a pacing electrode was sutured to the right atrium. Pacing at rates of 200 or 250 beats/min (10 animals per group) was performed for 15 min after base-line hemodynamic data had been obtained. At the end of the pacing period, a transmural biopsy was taken, frozen in liquid nitrogen, and sectioned into subepicardial, midmyocardial, and subendocardial layers. ATP, phosphocreatine, lactate, and glycogen were extracted and analyzed. Significant (P less than 0.001) transmural gradients of each of these metabolites existed in the control group. Pacing had no significant (P greater than 0.2) effect on any metabolite from layer to layer at 200 or 250 beats/min. However, indices of heart work (i.e., contractility (dP/dt), stroke work, and stroke volume) demonstrated significant reductions (P less than 0.01) due to pacing, while circumflex artery blood flow increased more than twofold (P less than 0.001) at the highest rate. These data suggest that physiologic autoregulation occurred during pacing and protected the subendocardium from stress-induced ischemic insult.
Relationship between colloid osmotic pressure and plasma protein concentration in the dog
Authors: Navar P. D. , Navar L. G.
Published: December 2017

This study was done to establish the correct relationship between protein concentration and plasma colloid osmotic pressure in the dog and to determine the possible influence of the relative albumin and globulin content (A:G ratio). Plasma samples from dogs, rats, and humans were evaluated for total protein concentration, globulin concentration, and colloid osmotic pressure. Samples were concentrated and diluted by ultrafiltration to provide a range of total protein concentrations from 1 to 12 g/dl. Rat and human plasma samples had A:G ratios of 1.4 and 2.1, respectively, and the relationship between protein concentration and colloid osmotic pressure was in agreement with the Landis-Pappenheimer equation. In contrast, dog plasma samples consistently exhibited lower colloid osmotic pressures for any given protein concentration. Two forms of empirical equations were derived to relate these parameters in the dog. Dog plasma samples had higher concentrations of globulin and the A:G ratio averaged 0.59 +/- 0.35 SD. There was a significant relationship between the A:G ratio and the plasma colloid osmotic pressure. Analysis of the possible effect of this altered relationship on glomerular filtration dynamics predicted that efferent plasma colloid osmotic pressure was not specifically affected and was dependent only on the filtration fraction and the plasma colloid osmotic pressure.
Radioimmunoassay of unprocessed sheep blood extracts to follow angiotensin metabolism
Authors: Osborn E. C. , Mackenzie J. C. , Rigby G. V. , Wilton A. , Sugden P. L.
Published: December 2017

The acceptability of radioimmunoassay to determine the levels of compounds antigenic to anti-angiotensin antibodies, in unprocessed methanolic blood extracts, was established for sheep blood. This approach was used to follow the clearance of antigenic compounds after administration of angiotensins I and II and fragments of angiotensin II in anesthetized sheep. The organs supplied by the systemic circulation and also the lungs effectively removed angiotensin I, but the removal of octapeptide occurred only in the peripheral tissues. The blood concentrations of compounds reacting with the anti-angiotensin II antibody always increased with passage of angiotensin I through the pulmonary circulation but not with passage of angiotensin II. The results indicate that factors other than efficiency of removal by the tissue is important in establishing blood levels. The sites of administration and of sampling were shown to be important in relation to ratios of the concentrations of antigenic material. There was a similar uptake of both hormones in the kidney; the relative inability of angiotensin I to reduce renal blood flow, therefore, does not result from a failure of uptake.
Altered hemodynamic responses to acute hypoxemia in spontaneously hypertensive rats
Authors: Walsh G. M. , Tsuchiya M. , Cox A. C. , Tobia A. J. , Frohlich E. D.
Published: December 2017

Conscious spontaneously hypertensive rats (SHR), 5--7 wk old, were studied hemodynamically by the direct Fick procedure to determine whether high total peripheral resistance (TPR) coexisted with increased oxygen consumption (QO2) at an early stage of hypertension development. Since under resting conditions cardiac output in SHR was not significantly different from normotensive controls, the elevated arterial pressure and QO2 were associated with increased TPR. Arterial hypoxemia was induced to reduce oxygen availability and to assess whether increased TPR in SHR could be reversed by this procedure. During hypoxemia, normotensive controls (WKY) responded with increased cardiac output and decreased arterial pressure and TPR. In contrast, arterial pressure and cardiac output fell in SHR; and the increased TPR persisted. QO2 fell in hypoxemic SHR demonstrating that the relationship between total body oxygen consumption and cardiac output was abnormal in young SHR, and that increased TPR in SHR was not dependent on resting levels of QO2 or oxygen availability. Although QO2 was elevated in SHR compared to age-matched WKY, this condition was not essential for maintained elevated vascular resistance.
Relation between cholinergic and histaminergic components in reflex vasodilatation in the dog
Authors: Rengo F. , Trimarco B. , Chiariello M. , Sacca L. , Violini R. , Rasetti G. , Ferro G.
Published: December 2017

Previous studies have shown that phentolamine is able to reverse the reflex vasodilatation produced by transitory baroreceptor stimulation by blocking sympathetic, histaminergic, and cholinergic components. A direct anticholinergic action of phentolamine has never been described; however, since it is known that this drug is capable of inhibiting histamine release during the reflex vasodilatation, it is possible that its ability to block the cholinergic component of the reflex is related to the latter property. Therefore, this study was undertaken in an attempt to identify possible relationships between cholinergic and histaminergic components of the reflex vasodilatation. Accordingly, in mongrel dogs the gracilis muscle was isolated and perfused and then loaded with 14C-labeled histamine. A transitory systemic hypertension was induced by intravenous injection of norepinephrine; this produced a reflex vasodilatation, shown by the fall in perfusion pressure, which was accompanied by an increase of histamine release from the muscle. Vagal block induced by atropine pretreatment reduced the fall in perfusion pressure induced by the systemic hypertension and produced a reduction of histamine release during the vasodilatation. In another group of animals a vasodilatation in the perfused muscle was induced by injection of acetylcholine. This response was accompanied by an increase in histamine release from the gracilis muscle. Alpha-receptor blockade, which has been shown to inhibit histamine release, reduced this acetyl-choline-induced vasodilatation. These results, while confirming the participation of the cholinergic system in the reflex vasodilatation elicited by transitory stimulation of the arterial baroreceptors, seem to demonstrate that this component is mediated almost exclusively by histamine release.
Ventricular morphology and pumping ability of exercised spontaneously hypertensive rats
Authors: Pfeffer M. A. , Ferrell B. A. , Pfeffer J. M. , Weiss A. K. , Fishbein M. C. , Frohlich E. D.
Published: December 2017

Spontaneously hypertensive rats (SHR) and two strains of normotensive Wistar rats were subjected to a 5 day/wk swimming program to determine whether the heart of the SHR could respond to an additional stimulus to cardiac growth. Swimming was tolerated well by all rats. Although body weight of the exercised groups was not significantly reduced, both the right and left ventricular weights of all exercised groups were increased. Left ventricular circumference and chamber volume were increased without a change in free wall thickness in all exercised groups. Ventricular performance was assessed by peak cardiac output and stroke volume attained during rapid intravenous volume loading, both before and after autonomic inhibition. After combined cholinergic and beta-adrenergic inhibition, all exercised rats had slower heart rates and higher peak stroke volume than respectively sedentary controls. Thus, exercised SHR had the same alterations in cardiac mass and performance as exercised normotensive rats. Despite the initial presence of left ventricular hypertrophy, the SHR responded appropriately to an additional stimulus for adaptive cardiac growth.
Effects of hemodynamic alterations on wall motion in the canine right ventricle
Authors: Santamore W. P. , Meier G. D. , Bove A. A.
Published: December 2017

Regional right ventricular (RV) wall motion was analyzed in six closed-chest, anesthetized, paced dogs by measuring distances between chronically implanted radiopaque markers on RV free wall and septum. Normally, contraction started in the sinus region 25 ms before conus region. Highest velocities of shortening occurred in the conus region (2.42 +/- 0.33 lengths/s) and in septum-to-free-wall direction (2.56 +/- 0.40 l/s). Percent shortening for all regions was between 12% and 17%. The data indicate that the RV ejects blood by a uniform reduction in its free wall surface area and septal-to-free-wall distance. Reduced venous return decreased end-diastolic length, percent shortening, maximum velocity of shortening, and time to end-systolic length. RV pressure overload increased end-diastolic length and decreased percent shortening and maximum velocity of shortening. LV pressure overload led to a nonhomogeneous contraction pattern. Percent shortening and maximum velocity of shortening increased in sinal and conal transverse directions and decreased in sinal and conal longitudinal directions; these changes indicate a mechanical interaction between RV and LV.
Exercise hyperemia in potassium-depleted dogs
Authors: Hazeyama Y. , Sparks H. V.
Published: December 2017

The experiments reported here are designed to evaluate the role of potassium (K+) in exercise hyperemia. Desoxycorticosterone acetate was implanted subcutaneously in six dogs, which were then placed on K+-deficient diets. Experiments were performed 3 or 4 wk later. Exercise vasodilation was much reduced in K+-depleted animals. However, when muscle stimulation caused very little vasodilation (i.e., in the most depleted animals) the muscle also produced little tension and extracted very little O2. O2 extraction was not limited by O2 availability. When the change in vascular resistance was plotted against O2 extraction, the data from K+-depleted dogs fell on a line constructed for control dogs. We conclude that the reduced exercise hyperemia of K+-depleted dogs is a result of reduced muscle O2 consumption rather than decreased K+ release. However, there was reduced vasodilation in response to brief tetanus and a loss of the triphasic initiation of exercise vasodilation with twitch work. This suggests that absence of K+ release does directly affect initiation of exercise vasodilation.
Cardiac performance: independent effects of inotropy and preload at high heart rate
Authors: Ilebekk A. , Miller M. M. , Kiil F.
Published: December 2017

Linear relationships between stroke volume (SV) and heart rate (HR) were observed during right atrial pacing in open-chest dogs at control inotropy, during intravenous isoproterenol infusion and during blood volume expansion by saline infusion at HR exceeding 150 beats/min. The slope of these relationships remained constant during variations in inotropy, but rose during blood volume expansion. Myocardial chord lengths in the anterior left ventricular wall were continuously recored by ultrasonic technique to estimate left ventricular volume. When heart rate was increased, end-diastolic volume decreased more rapidly after than before blood volume expansion, explaining the increased slope of the SV/HR relationship. The end-diastolic volume and the SV/HR relationship were not influenced by changes in inotropy. After blood volume expansion by 57 +/- 13%, control end-diastolic volume was reestablished by increasing heart rate 84 +/- 20 beats/min. At identical end-diastolic volume, SV was equal at different HR. Thus, the effects on SV of changes in preload and inotropy are separable during right atrial pacing, and SV is independent of HR at constant preload and adrenergic stimulation.
Chronic arteriovenous shunt: evaluation of a model for heart failure in rat
Authors: Flaim S. F. , Minteer W. J. , Nellis S. H. , Clark D. P.
Published: December 2017

A model for high output heart failure (HCO) was developed in male, Sprague-Dawley rats using an abdominal aortocaval shunt equal to 50% of total cardiac output (CO) with 2 mo of postsurgical recovery. The model was evaluated by analysis of hemodynamics, peripheral blood flows (BF) (radioactive microspheres), and plasma catecholamine levels as well as mass and fluid content of organs. In HCO, CO and left ventricular end-diastolic pressure were increased with significant left and right ventricular hypertrophy. Mean blood pressure (BP) was unchanged, but pulse BP was increased in HCO. BF to skeletal muscle, cutaneous, and some splanchnic regions was reduced to HCO, whereas BF to the cerebral, coronary, and renal beds was protected. Plasma epinephrine and norepinephrine levels were significantly elevated in HCO suggesting enhanced sympathetic as well as adrenal catecholamine release. Tissue analysis indicated altered circulatory status secondary to HCO in liver, kidney, spleen, and lung. The results indicate that this model will be a relevant tool for studies of the circulatory effects of heart failure.
Intestinal O2 uptake during sympathetic stimulation and partial arterial occlusion
Authors: Shepherd A. P.
Published: December 2017

In isolated loops of canine small bowel perfused at constant blood flow, stimulating perivascular sympathetic nerves (8--10 Hz) depressed O2 extraction and O2 uptake. Because sympathetic stimulation also decreased 86Rb extraction, the results confirmed earlier studies indicating that sympathetic stimulation closes "precapillary sphincters" and through diffusion limitations reduces the capillary-to-cell flux of oxygen. To determine if sympathetic stimulation could lower O2 uptake under more physiologic circumstances, a second series of experiments was performed during constant arterial pressure perfusion. Sympathetic stimulation reduced blood flow by about 30% in the steady phase. Oxygen extraction did not increase appreciably, so O2 uptake was also reduced. When partial arterial occlusion was used to lower the blood flow to the level that it reached during sympathetic stimulation, large increases (37%) in O2 extraction occurred so that O2 uptake remained near control levels. The results indicate that after arterial occlusion local mechanisms maintain O2 uptake by increasing O2 extraction through capillary density increases, but that this mechanism is impaired by sympathetic stimulation.
Transmural distribution of myocardial adenosine content during coronary constriction
Authors: Foley D. H. , Miller W. L. , Rubio R. , Berne R. M.
Published: December 2017

The transmural distribution of tissue adenosine content was determined in samples of the left ventricle of anesthetized open-chest dogs. Transmural tissue samples were obtained and quickly freeze-clamped during either normal coronary perfusion or partial constriction of the inflow tubing to the left common coronary artery. Inner, middle, and outer segments of the samples were assayed for adenosine, inosine, ATP, creatine phosphate, and lactate. In control experiments, there were no significant differences among the tissue contents of the substances in the three segments. However, during a 50.2 +/- 4.7% reduction of coronary inflow, adenosine content of inner, middle, and outer segments was 0.41 +/- 0.007, 0.030 +/- 0.006, and 0.016 +/- 0.003 nmol/mg protein, respectively. Outer segment content was significantly less than either middle or inner content. Lactate distribution was similar to that of adenosine, whereas ATP and creatine phosphate were lowest in the inner segment. Increases of the inner/outer adenosine ratio occurred when the coronary-ventricular pressure index was lower than 1.2. Thus, selective underperfusion of the subendocardium during reduced coronary inflow can result in greater accumulation of adenosine in that region.
Changes in ultrasonic attenuation indicative of early myocardial ischemic injury
Authors: Mimbs James W. , O'Donnell Matthew , Miller James G. , Sobel Burton E.
Published: December 2017

Page H340: James W. Mimbs, Matthew O'Donnell, James G. Miller, and Burton E. Sobel. “Changes in ultrasonic attenuation indicative of early myocardial ischemic injury.” Reprint requests should be addressed to J. W. Mimbs, Cardiovascular Division, Washington University, St. Louis, MO 63110.
Plasma catecholamine and blood pressure responses to sympathetic stimulation in pithed rats
Authors: Yamaguchi I. , Kopin I. J.
Published: December 2017

Sympathetic stimulation in pithed rats elicits increases in blood pressure (BP) and plasma levels of catecholamines. The BP is proportional to the logarithm of the plasma norepinephrine (NE) concentration. Adrenal medullectomy diminishes slightly only the initial phase of the BP responses, whereas bretylium blocks completely the BP response and diminishes by about 70% the increase in plasma NE. Adrenal medullectomy completely prevents the increase in plasma epinephrine (Epi) and diminishes by 30% plasma NE. Plasma levels of NE appear to reflect sympathetic neuronal activity, but the NE at sympathetic nerve endings is responsible for the increase in BP. Epi released from the adrenal medulla may enhance and accelerate the initial BP response, but plays only a minor role after the first 15 s.
Neurohumoral regulation of blood flow to bones and marrow
Authors: Gross P. M. , Heistad D. D. , Marcus M. L.
Published: December 2017

We used labeled microspheres to measure bone and marrow blood flow under control conditions and during several interventions. In dogs, blood flow to compact cortical bone (femoral diaphysis) was 2 +/- 0.1 ml.min-1. 100 g-1, and in hematopoietic marrow (femur), flow was 24 +/- 5 ml.min-1. 100 g-1. Hematopoietic cancellous bones (sternum, ilium) received substantial blood flow. We estimate that as much as 11% of cardiac output is directed to the skeleton. Bone and marrow vessels were responsive to several stimuli. During exercise, vascular resistance in bone increased two- to fourfold, in contrast to profound vasodilation in adjacent skeletal muscle. Hemmorrhage also increased bone vascular resistance. Bone and marrow vessels responded to humoral stimuli: norepinephrine increased vascular resistance and adenosine decreased resistance. Bone vessels also responded to neural stimuli: stimulation of carotid baroreceptors decreased vascular resistance, and activation of sympathetic pathways by baroreceptor deafferentation in cats increased vascular resistance. These studies indicate that bone and marrow vessels respond actively to physiological stresses and to several humoral and neurogenic stimuli
Myocardial performance and collateral flow after transient coronary occlusion in exercising dogs
Authors: Cohen M. V. , Yipintsoi T.
Published: December 2017

Fourteen dogs with prior constriction of the left circumflex (LCf) coronary artery were studied at rest and during treadmill running. Hemodynamics were measured before and after a 1-min LCf occlusion. Coronary and collateral flows were quantitated during occlusion both at rest and during exercise. Group I consisted of 4 dogs with resting collateral flow exceeding one-half (average 78%) of normal flow, and group II consisted of 10 dogs with collateral flows less than one-half (average 30%) of normal. At rest LCf occlusion caused no hemodynamic changes in group I, but stroke volume fell significantly in group II. During running, collateral flow after LCf occlusion doubled in group I, and there was only a small rise in left atrial pressure to 18 mmHg. In group II, collateral flow increased by 50% during running and actually decreased in 4 dogs. Significant cardiac failure developed as stroke volume halved, and left atrial pressure rose to an average 30 mmHg. Therefore exercise-induced depression of left ventricular function in the ischemic heart can be correlated to the amount of coronary collateral flow.
Arterial baroreflex control of heart rate in the conscious rat
Authors: Coleman T. G.
Published: December 2017

Angiotensin II, methoxamine and phenylephrine were evaluated in two tests of reflex responsiveness that involve arterial pressure increases (delta BP) and reflex bradycardia (delta HR). First, bolus injections produced comparable ratios (delta HR/delta BP, in beats . min-1 . mmHg-1) for the three agents: 1.69 +/- 0.31, 1.80 +/- 0.30, and 1.59 +/- 0.32, respectively (SE, n = 6). All three agents also had some undesirable direct chronotropic effects on the heart. Phenylephrine and methoxamine produced rapid and predictable pressure changes and were stable in solution. Blockade by atropine and propranolol was used to show that the bradycardia after bolus injection has an early component (1 s after pressure maximum) that is wholly parasympathetic. In the second test, 5-min infusions of the three agents produced comparable final delta HR/delta BP ratios: 2.0 +/- 0.3, 2.2 +/- 0.5, and 2.3 +/- 0.2 for angiotensin, methoxamine, and phenylephrine, respectively (n = 6). delta HR in this case had a predominant (estimated 67% of total) beta-adrenergic component. Therefore, rapid vagal control of heart rate in the conscious rat is temporary; it is replaced and strengthened in time by a more slowly developing beta-adrenergic component. Bolus injection and infusion of vasopressors can be conveniently used in combination to more fully quantitate heart rate responsiveness in conscious animals that have implanted arterial and venous catheters.
Effects of hematocrit variations on regional hemodynamics and oxygen transport in the dog
Authors: Fan F. C. , Chen R. Y. , Schuessler G. B. , Chien S.
Published: December 2017

The responses of alterations in regional hemodynamics and oxygen transport rate to hematocrit (Hct) were studied in 20 pentobarbitalized dogs. Hemodilution was carried out by isovolemic exchange with plasma in 12 dogs and the hemoconcentration with packed cells in 8 dogs. The cardiac output and regional blood flows were determined with the microsphere technique. In hemodilution, the increases of blood flow to the myocardium and the brain were out of proportion to the increase of cardiac output; the oxygen supply to the myocardium remained unchanged while that to the brain decreased only slightly. In hemoconcentration, vasodilation occurred in the myocardium and the brain to maintain constant oxygen supply. Splenic vessels had marked vasoconstriction with Hct alteration in either direction. Blood vessels in the liver, intestine, and kidney responded with a milder vasoconstriction and maintained a constant oxygen supply between Hct of 30-55%. Therefore, during Hct alteration, redistribution of blood flow to myocardium and brain occurred. The optimal Hct range for constant oxygen supply was different among various organs.
Left ventricular cannulation for microsphere estimation of rabbit renal blood flow
Authors: Bhattacharya J. , Beilin L. J.
Published: December 2017

When cannulation of the left ventricle and the left atrium were compared as methods for measuring for measuring renal blood flow distribution with radioactive microspheres in 9 conscious and 6 anesthetized rabbits, there were no differences between the two injection routes. Left ventricular cannulation per se did not affect cardiac output, nor the percentage of the cardiac output supplying the kidneys; but cardiac outputs estimated by thermodilution by injections via this route were up to 10% greater than those from left atrial injection. The advantages of left ventricular cannulation for experiments on regional blood flow distribution in conscious animals are discussed.
Reflex cardiac effects of local cutaneous cold exposure in dogs
Authors: Borgia J. F. , Horvath S. M.
Published: December 2017

Cardiovascular responses initiated by local cutaneous cooling were evaluated in 16 anesthetized dogs of which 8 were pretreated with propranolol. Heart rate, cardiac index (CI), and indices of ventricular contractility were significantly elevated in untreated animals during cold stimulation. Myocardial oxygen uptake (MVo2) and left ventricular work (LVW) were also increased, and cardiac mechanical efficiency was significantly reduced. Total peripheral vascular resistance remained unchanged. In the propranolol group, heart rate decreased by 12 beats/min, but CI was maintained constant during cold by a rise in stroke index. Left ventricular dP/dtmax was reduced and ventricular preload elevated, but LVW, MVo2, and cardiac efficiency were unchanged. These data indicate that local cutaneous cooling increases myocardial oxygen demand by reflexly elevating heart rate and cardiac contractility rather than by increasing cardiac afterload. The response is completely eliminated by beta-adrenergic blockade. The significance of these observations in regard to the cold-intolerant individual with coronary disease is discussed.
Elimination of noise in telemetry systems by pulse-width discriminator
Authors: Livnat A. , Johnson R. P. , Zehr J. E.
Published: December 2017

A pulse-width-discriminator circuit (PWD) was developed and applied for noise reduction in an FM pulse-interval-ratio modulation telemetry system. The PWD was incorporated as an intermediary between the tuner and the demodulator. The application of the circuit as a noise filter is a result of its ability to distinguish between pulses of different durations and its ability to eliminate pulses whose durations are less than some predetermined value. Since spikes of radio-frequency interference (RFI) occurring at the tuner output were of significantly shorter duration than the encoding pulses, they were virtually eliminated by the PWD. This prevented false triggering of the demodulator and resulted in a noise-free final demodulated output signal. This system was tested during telemetered blood pressure measurements in an unrestrained dog and proved to be extremely effective in eliminating spurious noise caused by electromagnetic interference in the radio-frequency range.
Active and passive mechanical characteristics of bovine mesenteric lymphatics
Authors: Ohhashi T. , Azuma T. , Sakaguchi M.
Published: December 2017

Pressure-volume and pressure-radius relationships in lymphangions isolated from bovine mesenteric lymphatics were similar in pattern with those in the vein. Circumferential modulus of elasticity of the lymphatics ranged from 4.2 x 10(4) tatic walls. The contractile force increased in early stages of distension and decreased after an optimal intraluminal pressure was attained. The spontaneous activity was also affected by the rate of wall deformation. The pacemaker site of spontaneous activity seemed to be in the wall in the immediate vicinity of the inlet valve of a lymphangion. The activity propagated with a velocity of 4-5 mm/s. Ejection fraction of a lymphangion was between 45 and 65%. The endurance limit of the lymphatic valve was 68.4 +/- 7.6 cmH2O in specimens of about 3 mm in outer diameter. These findings suggested that lymphatic smooth muscle seemed to play a major role in elastic behavior of the wall and in regulation of the spontaneous activity, thereby affecting significantly passive and active lymph transport.
Inhibition by adenosine of catecholamine-induced increase in rat atrial contractility
Authors: Rockoff J. B. , Dobson J. G.
Published: December 2017

Because adenosine has been shown to attenuate the catecholamine-induced increase in myocardial cAMP formation and glycogen phosphorylase activity (Circ. Res. 43: 785-792, 1978), the present study was undertaken to determine whether the nucleoside inhibits the catecholamine-elicited increase in cardiac contractile state. Isolated rat atria were bathed in oxygenated physiologic saline and stimulated to contract isometrically at 2/s. Isoproterenol (0.1 microM) increased peak contractile force (PCF) by 96% and the rate of force development (+dF/dt) by 107%. Adenosine (10 microM) alone had no effect on these contractile parameters. Isoproterenol in the presence of adenosine increased PCF and +dF/dt only 15 and 14%, respectively. Elevation of bathing medium Ca2+ or administration of dibutyryl cAMP (DBcAMP) increased PCF and +dF/dt, but these responses were not decreased by adenosine. Inosine, adenine, adenosine 5'-monophosphate, and guanosine inhibited the isoproterenol-induced responses 5-22%. The results indicate that adenosine markedly inhibits, whereas some related purines only mildly attenuate, the catecholamine-elicited, but not the Ca2+- or DBcAMP-elicited, increases in contractility. Thus, adenosine may antagonize catecholamine-elicited glycogenolysis and enhanced contractile state in the heart by exerting an effect at the level of, or proximal to, cAMP formation.
Cardiovascular effects of acute hemorrhage in fetal lambs
Authors: Toubas P. L. , Silverman N. H. , Heymann M. A. , Rudolph A. M.
Published: December 2017

The effects of acute hemorrhage were studied in two groups each with six fetal lambs (100-116 amd 128-147 days gestation) 3-4 days after we implanted catheters. Fetal blood pressures, heart rate, arterial blood gases and pH, and combined ventricular output and its distribution (radionuclide-labeled microsphere technique) were measured before and 5 min after removal of 15% of fetal-placental blood volume measured by 125I-albumin dilution. Because there were no differences in responses in the two age groups, the data were pooled. Fetal arterial mean pressure fell significantly (50.7 +/- 2.5 to 45.5 +/- 2.6 mmHg) as did heart rate (186 +/- 6 to 151 +/- 13 beats/min) and arterial blood pH (7.39 +/- 0.02 to 7.30 +/- 0.02); arterial blood carbon dioxide tension rose (39.7 +/- 29 to 44.1 +/- 4.4). Combined ventricular output fell from 610 +/- 58 to 448 +/- 45 ml . kg-1 . min-1 (P < 0.05). Blood flow to the umbilical-placental circulation, as well as to the fetal body, fell significantly. Blood flow to the kidneys, gastrointestinal tracts, and lungs also fell, but flow to other organs was maintained. Blood volume reduction in the fetus markedly influences blood gas exchange, because it results in a reduction of umbilical-placental blood flow associated with the fall in arterial pressure.
A vasoconstrictor cardiogenic chemoreflex induced by prostaglandin F2 alpha
Authors: Parker R. E. , Strandhoy J. W.
Published: December 2017

Systemic and skeletal muscle vascular responses to intracardiac prostaglandin F2 alpha (PGF2 alpha) were studied in anesthetized dogs. Resistance changes in a vascularly isolated but innervated reservoir-perfused gracilis muscle could occur only neurogenically. Injection of PGF2 alpha or serotonin (5-HT) raised systemic arterial blood pressure (BP) and caused reflex increases in gracilis muscle perfusion pressure (GMPP) that were abolished by alpha-adrenergic blockade. These changes in GMPP are opposite to the expected baroreceptor responses to an increase in BP. Subepicardial local anesthesia attenuated both delta BP and delta GMPP to 5-HT but only the delta GMPP to PGF2 alpha. Changes in BP and GMPP to 5-HT were reduced by vagotomy but not by stellate ganglionectomy. Conversely, stellate ganglionectomy significantly reduced the delta GMPP to PGF2 alpha but not the delta BP. Vagotomy affected neither delta BP nor delta GMPP following PGF2 alpha. Thus, while PGF2 alpha and 5-HT produce reflex vasoconstriction in gracilis muscle that is mediated through sympathetic efferent nerves and initiated by cardiogenic reflexes, apparently PGF2 alpha does so through sympathetic afferent and 5-HT through vagal afferent pathways. Further, since the systemic pressor response to PGF2 alpha persisted after stellatectomy, vagotomy, or local anesthesia, it is independent of the sympathetic cardiogenic chemoreflex.
Baroreceptor output during normal and obstructed breathing and Mueller maneuvers
Authors: Fitzgerald R. S. , Robotham J. L. , Anand A.
Published: December 2017

Cardiovascular control during asthma and other forms of obstructed breathing has not been extensively investigated. Previous studies in dogs have shown that obstructed breathing or an inspiratory effort against a blocked airway (Mueller maneuver) provoke large oscillations in blood pressure. During the inspiratory phase transmural systolic pressure relative to atmosphere drops initially, but transmural systolic pressure relative to intrathoracic pressure can remain unchanged or even increase. Because the carotid baroreceptors are located in the extrathoracic circulation, whereas the aortic baroreceptors are located in the intrathoracic circulation, and each responds to local transmural arterial pressure, simultaneous baroreceptor output from these two areas was measured in the anesthetized cat during normal and obstructed breathing and during Mueller maneuvers. Both whole-nerve and single-fiber preparations showed a significantly decreased output from the carotid baroreceptors during obstructed inspiratory efforts, whereas aortic baroreceptor output decreased significantly less or not at all. Transmural systolic pressure decreased significantly less in the aorta than in the carotid regions. Further, the aortic baroreceptors were more sensitive to changes in pulse pressure than were the carotid baroreceptors. These results suggest a mechanism for stabilizing the cardiac responses to precipitous falls in blood pressure that occur in obstructed breathing.
Adult cardiac myocytes in primary culture: cell characteristics and insulin-receptor interaction
Authors: Eckel J. , van Echten G. , Reinauer H.
Published: December 2017

Calcium-tolerant adult cardiac myocytes were kept in culture under serum-free conditions in the presence of physiological concentrations of insulin. Up to 4 days, 70% of cells retained their in vivo rodshaped morphology without gross structural alterations. During that period a constant ATP-to-ADP ratio was observed with a mean value of 10.6 +/- 0.5 (n = 4). The rate of [14C]phenylalanine incorporation remained unaltered up to 63 h in culture. Insulin binding to cultured cells was found to be time-and temperature-dependent, reversible, and highly specific. Scatchard analysis of equilibrium binding data showed a curvilinear plot with a high-affinity segment yielding an apparent dissociation constant of 4.5 X 10(-10) mol/l and a receptor number of 125,000 sites/cell. Both affinity and receptor number remained unaltered between 18 and 66 h in culture. [14C]phenylalanine incorporation was stimulated by 108% in cardiocytes cultured in the presence of high concentrations of insulin (1.7 X 10(-7) mol/l) for 63 h, when compared with control cells cultured in the absence of insulin. These data demonstrate the retention of structural integrity, insulin receptors, and insulin responsiveness in primary cultured adult cardiac myocytes and provide a useful model for long-term studies on the regulation of insulin action on the heart.
Effect of vibration on a canine cutaneous artery
Authors: Lindblad L. E. , Lorenz R. R. , Shepherd J. T. , Vanhoutte P. M.
Published: December 2017

Vibration of rings of isolated canine saphenous arteries depressed contractions induced by potassium chloride, prostaglandin F2 alpha, and activation of the adrenergic nerve endings by electrical stimulation. Peak contractions to exogenous norepinephrine were not significantly affected by vibration, being augmented, unchanged, or depressed, whereas contractions during the stable plateau phase were depressed. The calcium entry blocker diltiazem reduced the peak response but not the stable plateau phase of the contraction to norepinephrine; in the presence of diltiazem, vibration still depressed the latter. When vibration was applied during the steady state of contractions evoked by electrical stimulation, the depression was immediate, and its extent increased with both the amplitude (0.025-0.10 mm) and the frequency (30-150 Hz) of vibration. In arteries labeled with [3H]norepinephrine, vibration (120 Hz, 0.1 mm amplitude) during electrical stimulation induced a slight but significant increase in the release of labeled transmitter. It is suggested that the depression of contractions to potassium ions, prostaglandin F2 alpha, sympathetic nerve stimulation, and the plateau phase of the response to exogenous norepinephrine are caused by vibration depressing the force-generating process in vascular smooth muscle. Failure of vibration to significantly depress the peak contraction to norepinephrine may be explained by the facilitation by vibration of the influx of extracellular calcium ions.