bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium-Dependent Action Potentials Produced by Catecholamines in Guinea Pig Atrial Muscle Fibers Depolarized by Potassium
Authors: PAPPANO ACHILLES J.
Published: June 2012

Atrial muscle fibers of the guinea pig were depolarized and rendered inexcitable by elevation of [K
+
]
o
to 22 m
M
. Isoproterenol, epinephrine, and norepinephrine restored propagated action potentials and contractions to atrial cells without changing the resting potential. The peak value of the intracellularly recorded action potentials varied 28 mv for a 10-fold change in [Ca
2+
]
o
. Isoproterenol-induced restoration of action potentials was insensitive to large concentrations of tetrodotoxin (3 x 10
-6
M
) but antagonized by Mn
2+
(0.2 m
M
). These data supported the proposal that the catecholamines restored excitability by increasing membrane conductance to Ca
2+
. In addition to the catecholamines, the divalent cations Ba
2+
, Sr
2+
, and Ca
2+
restored action potentials to atrial muscle fibers depolarized by elevated K
+
. The effectiveness of the divalent ions in allowing action potentials was inversely related to the estimated hydrated ionic radii. Like the action potentials observed in the presence of isoproterenol, those permitted by Ba
2+
, Sr
2+
, and Ca
2+
were prevented by Mn
2+
but insensitive to blockade by tetrodotoxin.
Effect of Alterations in the Stimulus Rate upon Energy Output, Tension Development and Tension-Time Integral of Cardiac Muscle in Rabbits
Authors: GIBBS C. L. , GIBSON W. R.
Published: June 2012

The effect of stimulus rate on the isometric energy output of rabbit papillary muscle at room temperature was examined by a myothermic technique. The stimulus rates used were: 1 per 1.5, 2.0, 3.0, 7.0 and 10.0 seconds. Mechanical output at any given rate was varied by altering muscle length. Both peak tension and the time integral of tension were used as mechanical variables against which isometric heat production was plotted. The relationship between heat and peak tension was curvilinear, whereas that between heat and the time integral of tension was rectilinear. Statistically either mechanical index was equally good at predicting isometric heat production. Changes in the stimulus rate did not affect any of the parameters (intercept, slope, curvature) of the polynomials relating heat to tension but increasing the stimulus rate did significantly raise the slope of the relationships between heat and the time integral of tension. The magnitude of the tension-independent heat rose from .596 mcal/g muscle at a stimulus rate of 1 per 10 seconds to 0.744 mcal/g at a rate of 1 per 1.5 seconds.
Direct Current Make and Break Thresholds for Pacemaker Electrodes on the Canine Ventricle
Authors: DEKKER EGBART
Published: June 2012

Thresholds to anodal make, anodal break, cathodal make and cathodal break have been studied throughout the cardiac cycle in 13 dogs under pentobarbital anesthesia.

Unipolar direct current pulses were applied through epicardial pacemaker electrodes to the left ventricle. Make and break responses were separated by letting the break and make occur in the refractory periods of the following and preceding cycle, respectively.

Four distinct threshold interval curves were obtained from each of 17 electrodes. The anodal break and cathodal break curves showed an early diastolic dip. Dips were deepest in the anodal break curves. These also had the shortest effective refractory period. Thresholds for cathodal make and anodal make first dipped steeply, then gradually sloped down towards end-diastolic levels. The magnitude of end-diastolic mean threshold values increased in the following order: cathodal make, anodal make, cathodal break, anodal break.

Comparison of threshold interval curves for make and break responses with those for shorter rectangular anodal and cathodal curves throughout the cardiac cycle supports the hypothesis that the threshold behavior to a short rectangular pulse is determined by whichever of two thresholdsis lowest: make or break at that particular cycle interval.
Effects of Blood Pressure and Blood Viscosity on Fluorescein Transit Time in the Cerebral Microcirculation in the Mouse
Authors: ROSENBLUM WILLIAM I.
Published: June 2012

Fluorescein transit time from pial arterioles to pial venules was measured in the mouse by analyzing motion pictures taken at 40 frames/sec. Increased blood pressure reduced the transit time. Increased blood viscosity lengthened the transit time. Viscosity was increased by rendering the animals polycythemic, or by infusions of high molecular weight dextran. Two different dextrans were used. The one with the higher molecular weight (500,000) produced a higher viscosity and a more prolonged transit time than the one with the lower molecular weight (250,000). These dextrans produced a prolongation of the transit time equal to that, or greater than that, observed in the polycythemic animals, even though whole blood viscosity in polycythemia exceeded that of the dextran treated mice over a wide range of physiologically pertinent shear rates applied in vitro in a rotational viscometer. Results indicate that increases of blood viscosity produce decreases in the velocity of the plasma, and that viscosity increments brought about by raising the hematocrit, may be less effective than viscosity increments brought about by raising the viscosity of the plasma.
Cardiovascular Reflexes from Stretch of Pulmonary Vein-Atrial Junctions in the Dog
Authors: EDIS ANTHONY J. , DONALD DAVID E. , SHEPHERD JOHN T.
Published: June 2012

The reflex cardiovascular response to stretch of left pulmonary vein-atrial junctions was studied in anesthetized dogs in which both aortic nerves were cut and the carotid sinuses were isolated vascularly. After thoracotomy, the root of the left lung was tied and a small Silastic balloon (1.5-cm long), attached to a nylon catheter, was inserted into each of the three left pulmonary veins and tied so that its tip lay at the junction of the vein with the left atrium. In six dogs, heart rate response to balloon distension of 2.0 ml was studied over a range of initial heart rates (75 to 240 beats/min) achieved by varying the carotid sinus pressure. On distension of the balloons, slowing occurred if the initial heart rate was > 140 to 150 beats/min and acceleration if it were less. In eight dogs, aortic blood pressure and cardiac output measured before, during, and after balloon distension (0.25 to 2.0 ml) demonstrated a hyperbolic relationship between balloon volume and decrease in calculated systemic vascular resistance. All responses were abolished by vagotomy. The reflex vasodilatation was sustained and caused by decreased adrenergic activity; the reflex bradycardia or tachycardia was due to interplay of vagal and sympathetic cardiac efferents.
Neurotransmitter Control of Sinoatrial Pacemaker Frequency in Isolated Rat Atria and in Intact Rabbits
Authors: GRODNER ALBERT S. , LAHRTZ HANS-GUNTHER , POOL PETER E. , BRAUNWALD EUGENE
Published: June 2012

The sinoatrial node is under the control of both parasympathetic and sympathetic influences. To study the interaction between these opposing influences, the response of the frequency of contraction of a spontaneously contracting rat right atrium to combinations of the neurotransmitters, norepinephrine and acetylcholine was observed. Norepinephrine in concentrations of 1 x 10
-7
M, 1 x 10
-6
M, and 1 x 10
-5
M, which by themselves increased atrial frequency by averages of 30%, 51% and 82%, respectively, and acetylcholine in concentrations of 1 x 10
-5
M, 1 x l0
-4
M, and 1 x 10
-3
M, which by themselves decreased atrial frequency by averages of 17%, 52%, and 97%, respectively, were added in all combinations to the atrial preparations. The response was not an algebraic sum of the effects of each of the agents; rather, the bradycrotic influence of acetylcholine predominated in all cases. This action of acetylcholine was blocked by atropine. To evaluate this interaction under more physiologic circumstances, the response of heart rate of anesthetized rabbits to isoproterenol, a potent beta-receptor stimulant, and to asphyxia, a stimulus which produces a marked parasympathetic discharge, was studied. Asphyxia alone induced a marked bradycardia that could be abolished by vagotomy. However, this bradycardia was not prevented by isoproterenol. It is concluded that the predominance of the parasympathetic nervous system on the sinoatrial frequency is a result of the interaction of the neurotransmitters, norepinephrine and acetylcholine on the sinoatrial node. In this interaction the presence of acetylcholine appears to prevent the action of norepinephrine.
Activation of Lipoprotein Lipase
Authors: WHAYNE THOMAS F. , FELTS JAMES M.
Published: June 2012

Guinea pig serum is deficient in high density lipoproteins (HDL); post-heparin lipoprotein lipase (LPL) from it hydrolyzes a triglyceride (TG) emulsion very slowly. The rate is markedly increased by the addition of rat serum and even further by rat serum plus heparin. We have studied further the activation of LPL in this system. Rat serum lipoprotein fractions were isolated by ultracentrifugation and added to guinea pig postheparin serum in the presence or absence of heparin. When added in proportion to their original serum concentrations, HDL caused the greatest increase in TG hydrolysis. When each fraction was added at equal protein concentrations, purified low density lipoproteins had almost no effect; both very low density lipoproteins and HDL were very effective in increasing the rate of hydrolysis. Rat serum or rat HDL, added to the assay system in increasing amounts, appeared to increase the effective substrate concentration. In the absence of heparin, increasing the concentration of HDL increased the reaction rate which approached a limiting velocity (V
max
) and produced a hyperbolic curve which conformed to Michaelis-Menten kinetics. In the presence of heparin, increasing the concentration of HDL produced an S-shaped curve and increased the V
max
. These data conformed to the sigmoidal kinetics described by the Hill equation. Our results suggest that (1) heparin may function as a specific ligand which acts as an allosteric modifier of LPL and alters the kinetics of interaction of LPL with the effective substrate and (2) the rate of hydrolysis of the effective TG substrate is regulated by the concentration of this substrate.
Digitalis-Induced Bundle-Branch Ventricular Tachycardia Studied by Electrode Catheter Recordings of the Specialized Conducting Tissues of the Dog
Authors: DAMATO ANTHONY N. , LAU SUN H. , BOBB GUSTAVUS A.
Published: June 2012

Electrode catheter recordings of the bundle of His (H), the right bundle branch (RB) and the left bundle branch (LB) were obtained in 15 dogs without thoracotomy during sinus rhythm and digitalis-induced ventricular tachycardia. During sinus rhythm an H-RB-LB sequence was recorded. This sequence was unchanged during atrial stimulation at rapid rates or during cardiac slowing by vagal stimulation. In 10 of 15 cases of digitalis-induced ventricular tachycardia the LB potential preceded the onset of ventricular depolarization (QRS), and an LB-H-RB sequence was recorded. These findings indicated that during ventricular tachycardia the pacemaker was located in the left bundle branch and the bundle of His was retrogradely depolarized. In 5 of 15 cases of digitalis-induced ventricular tachycardia the H, LB and RB potentials were recorded after the onset of ventricular depolarization. These findings suggested that the pacemaker was located in the Purkinje fibers.
Electrophysiological Characteristics of Canine Atrial Plateau Fibers
Authors: HOGAN PERRY M. , DAVIS LARRY D.
Published: June 2012

Right atria from dog hearts were immersed in Tyrode's solution with the endocardial surface of the anterior wall exposed. Glass microelectrodes were used to impale fibers in different anatomical areas of this preparation. Electrical characteristics of atrial plateau fibers located along the caval border of the crista terminalis were compared with those of regular atrial fibers from other sites. The former conducted at a rate (0.803±0.110 M/sec) two to three times more rapidly than pathways composed of regular atrial fibers. A period of supernormal excitability was demonstrated for plateau fibers but not for regular fibers. Graded premature responses could be elicited in plateau fibers by both electrical stimulation and propagated action potentials. Duration of the effective refractory period of plateau fibers (196.1±2.5 msec) was longer than that of regular fibers (147.8±5.4 msec). Plateau fibers required a lower level of membrane potential (-62.1 ± 0.8 mv) to generate a propagated action potential than did regular fibers (-65.5 ± 1.3 mv). Regular atrial fibers could respond at faster rates to high frequency stimulation than plateau fibers.
Beta-Receptor Blockade and Myocardial Effects of Cardiac Glycosides
Authors: KOCH-WESER JAN
Published: June 2012

Because of suggestions that norepinephrine release from cardiac sympathetic nerves contributes to the myocardial action of digitalis, the effect of betareceptor blockade on these actions was determined. 10
-6
M
propranolol did not alter the basal contractility of isolated kitten papillary muscles or of atrial strips from kittens, guinea pigs, rabbits, dogs, and chickens but decreased by 85% their inotropic response to norepinephrine released by tyramine or highintensity electrical stimulation. The same concentration of propranolol had no effect on cumulative inotropic concentration-effect curves for ouabain, acetylstrophanthidin, and digoxin in these preparations. Presence of propranolol did not modify the actions of cardiac glycosides on the time course of isometric contraction. Beta-receptor blockade was without effect on decreases in active tension and increases in resting tension induced by toxic concentrations of cardioactive steroids. The frequency of digitalis-induced automaticity in guinea pig atrial strips and kitten papillary muscles was significantly decreased by propranolol, presumably because of its direct electrophysiologic actions. Exposure of cat hearts to digoxin in vivo and to ouabain in vitro had no effect on myocardial norepinephrine concentrations. It is concluded that release of myocardial norepinephrine plays no role in the actions of cardiac glycosides on the heart.
Fourier Analysis of Left Ventricular Performance
Authors: ABEL FRANCIS L.
Published: June 2012

Fourier analysis has been applied to simultaneously obtained ventricular pressure, ascending aortic pressure, and aortic flow in the closed- and open- chest dog and during infusion with isoproterenol, norepinephrine, and phenylephrine. Partial measurements were also obtained from a sheep and a primate. Impedance moduli and phases were calculated from the ventricular (forcing) and aortic (input) side of the aortic valve and compared. Forcing impedance was similar in form but larger than input impedance, and the phase became positive earlier. Ventricular and aortic powers were calculated and expressed as pressure power, kinetic energy power, and reactive power, along with their harmonic distributions. Mean pressure represented 80 to 91% of total load power but only 20 to 51% of total ventricular power. Calculated efficiency varied from 35% with isoproterenol infusion to 100% with norepinephrine, phenylephrine, and open-chest states. Control efficiency was 78%. The concept of impedance matching was investigated; maximal efficiency occurred with optimal matching. Internal resistance was shown to represent an easily measurable quantity which also partially corresponds to the more complex impedance measurement.
Functional Characteristics of the Gating Mechanism in the Canine A-V Conducting System
Authors: MYERBURG ROBERT J. , GELBAND HENRY , HOFFMAN BRIAN F.
Published: June 2012

The areas of maximum action potential duration, or gates, of the isolated canine distal A-V conducting system were studied by microelectrode techniques to determine the characteristics of their responses to premature impulses and to rapid rates of stimulation. The results indicate that premature responses will be conducted at the same velocity as driven responses until the coupling interval between the driven and premature impulses approaches the refractory period of the gate. When delayed conduction of the premature impulse develops, it occurs over a segment of the conducting system incorporating the gate. The magnitude of the delay which can develop at coupling intervals just in excess of the functional refractory period tends to be small in healthy tissue and larger in depressed tissue. Suitable delays allowed premature impulses having coupling intervals shorter than the refractory period at the gate to be conducted distally. The refractory period in response to rapid rates of stimulation was discordant in the several false tendons in six of nine preparations studied. Both delayed conduction and 2:1 conduction were shown to occur near the limit of response to rapid stimulation. The data presented suggest certain functional analogies between the A-V node and the gating mechanism.
Mechanical Properties of Rat Cardiac Muscle during Experimental Hypertrophy
Authors: BING OSCAR H. L. , MATSUSHITA SATORU , FANBURG BARRY L. , LEVINE HERBERT J.
Published: June 2012

The mechanical properties of trabecular muscles from the hearts of 77 rats subjected to aortic arch constriction were compared with those from 77 unoperated and sham-operated control animals at 1, 3, 7, 14, and 28 days after operation. Significant hypertrophy, as evidenced by an increase in left ventricle to body weight ratio, was first seen at three days (
P
< 0.02), reached a maximum of 30 to 40% by seven days (
P
< 0.001), and remained relatively constant throughout the remainder of the experiment. Depression of isotonic shortening velocity and maximum isometric force of trabecular muscles from hypertrophied hearts was first seen at seven days. These changes persisted at 14 and 28 days. When alterations in muscle mechanics due to changes in muscle thickness were taken into consideration, muscles from hypertrophied hearts demonstrated a depressed maximum velocity of shortening (
P
< 0.001), while development of isometric tension was unaltered. The latter appeared to be maintained at least in part by a prolonged contraction time, as reflected by increases in the time to peak isometric tension (
P
< 0.05) and the time to peak "unloaded" isotonic shortening (
P
< 0.001). Resting tension was increased in trabecular muscles from hypertrophied hearts. Tissue hydroxyproline concentration was elevated with hypertrophy. The observed depression in muscle shortening velocity at light loads may be explained by altered contractile state or by increased stiffness of the parallel elastic element.
Influence of Extracellular Potassium Concentration on Myocardial Uptake and Inotropic Effect of Tritiated Digoxin
Authors: PRINDLE KIRK H. , SKELTON C. LYNN , EPSTEIN STEPHEN E. , MARCUS FRANK I.
Published: June 2012

Because of conflicting reports on the influence of extracellular potassium concentration ([K]
0
) on the inotropic action of cardiac glycosides, we compared the effects of varying [K]
0
(1.5, 4.5, and 7.5m
M
) on the inotropic action and myocardial concentration of tritiated digoxin (5 x 10
-7
M
) using the isolated cat papillary muscle. The time course of the inotropic response to digoxin was significantly altered by [K]
0
in an inverse manner; the rate of change of the active tension response to digoxin (g/mm
2
· min
-1
) was 0.048±0.004 with low [K]
0
, 0.025±0.003 with normal [K]
0
and 0.014±0.002 with high [K]
0
. There were no differences, however, in the peak inotropic responses achieved at each [K]
0
. Muscles were analyzed for
3
H-digoxin content after 45 minutes, and at the time of the peak inotropic response. The relationships found between [K]
0
and
3
H-digoxin content were similar to those found between [K]
0
and active tension. Moreover, a significant positive correlation between digoxin content and the increment in active tension was observed. Thus, an inverse relationship exists between [K]
0
and the rate of development of the inotropic response to digoxin, changes that may be due to a [K]
0
induced alteration in myocardial digoxin content.
Circus Movement within the AV Node as a Basis for Supraventricular Tachycardia as Shown by Multiple Microelectrode Recording in the Isolated Rabbit Heart
Authors: JANSE M. J. , VAN CAPELLE F. J. , FREUD G. E. , DURRER D.
Published: June 2012

Supraventricular tachycardia in an isolated rabbit heart preparation was repeatedly initiated and terminated by carefully timed atrial premature beats. Transmembrane action potentials of AV nodal cells were recorded simultaneously by a "brush electrode" consisting of 10 microelectrodes. Surface electrograms of atrium and His bundle were also recorded. The moments of activation of 54 different AV nodal cells, both during regular driving of the atrium and during tachycardia were ascertained. Premature atrial beats introduced during tachycardia would either "reset" the tachycardia or terminate it. The sequence of activation of the AV nodal cells when initiating tachycardia, during tachycardia itself, and when premature beats were interpolated during tachycardia warrant the conclusion that a circus movement in the AV node, based on functional longitudinal dissociation of the upper AV node, was the underlying mechanism of the arrhythmia.
Activation of Lipoprotein Lipase
Authors: WHAYNE THOMAS F. , FELTS JAMES M.
Published: June 2012

Lipoprotein lipase (LPL) from rat heart acetone powders has been reported to depend on the presence of NH
4
+
, calcium, or other divalent cations for optimal activity. In addition, the enzyme will not hydrolyze an artificial triglyceride emulsion unless it is converted to an active substrate by the addition of very low density lipoproteins, high density lipoproteins (HDL), or certain peptides contained in these complexes. We observed earlier that HDL that had been extensively dialyzed against 0.005M ethylenediaminetetraacetic acid (EDTA), which probably removed most of the divalent cations, produced little lipolytic activity in LPL from rat heart acetone powders. This observation led us to evaluate the cation requirements for LPL. LPL was prepared in soluble form from rat heart acetone powders. HDL was isolated from rat serum by ultracentrifugation. The assay system contained a phospholipid-stabilized triglyceride emulsion as substrate. The addition of the whole rat serum to the LPL assay system produced high LPL activity. The addition of dialyzed HDL isolated from the same volume of serum produced low LPL activity. The addition of calcium in physiological concentration to the assay containing HDL increased LPL activity markedly. The high enzyme activity produced by both serum and HDL plus calcium was inhibited by ethyleneglycol bis(β-aminoethylether)-N,N'-tetraacetic acid (EGTA), a specific calcium chelating agent. The addition of NH
4
+
or magnesium at several concentrations did not replace calcium in stimulating LPL activity. We conclude that calcium has a cofactor function in the LPL lipolytic reaction and that the optimal enzyme reaction rate is attained in the presence of calcium concentrations found in serum.
Elastic Deformation in Orthotropic Vessels
Authors: MELBIN JULIUS , NOORDERGRAAF ABRAHAM
Published: June 2012

Excursions of the semiaxes were used to define the distortion and shape of the vessel cross section considered for conic and almost conic models. Some describing functions and mensuration expressions closely approximate, yet greatly simplify, calculations of perimeter and cross sections. Theory and experiments with models were in good agreement, but preliminary experiments showed the real case to be more complicated. Physical properties of the pulmonary trunk varied along its axis, growing stiffer toward the periphery. Furthermore, the dimension variations with transmural loading alter concepts of properties derived from measurements of a single diameter. The influence of the pericardium on the deformation of the main pulmonary artery under transmural stress was also explored. It was seen that the pericardium exerts significant restraint on the distortion and volume variations of this vessel. Over normal pressure ranges, removal of the pericardium can result in trunk volumes up to 100% greater than realized with the pericardium intact.
Giucagon in Prevention and Abolition of Ouabain-Induced Ventricular Tachycardia in Normokalemic and Hypokalemic Dogs
Authors: Einzig Stanley , Todd Edward P. , Nicoloff Demetre M. , Lucas Russell V.
Published: June 2012

A recent study suggested that glucagon has antiarrhythmic properties in addition to its positive inotropic effect. The present study was designed to evaluate the efficacy of glucagon in preventing and converting ouabain-induced ventricular tachycardia (VT) in normokalemic and hypokalemic dogs. Paired studies were made in ten normokalemic dogs and in eight dogs rendered hypokalemic by diet and hydrochlorothiazide. All dogs were pretreated with glucagon, and the amount of ouabain required to produce VT was measured. Each dog served as its own control in a second study in which normal saline was substituted for glucagon. When VT was produced during the control study, the response to a bolus injection of glucagon was evaluated. (1) Pretreatment with glucagon delayed the appearance of VT in hypokalemic dogs but not in normokalemic dogs. (2) Glucagon, by bolus injection, converted VT to sinus rhythm in 78% of the normokalemic dogs and in 100% of the hypokalemic dogs. (3) The mechanisms by which glucagon exerts its antiarrhythmic effect are not clearly defined.
Intracortical Distribution of Renal Blood Flow in Hemorrhagic Shock in Dogs
Authors: Logan Alexander , Jose Pedro , Eisner Gilbert , Lilienfield Lawrence , Slotkoff Lawrence
Published: June 2012

The effect of acute hypotensive hemorrhage on the intracortical distribution of renal blood flow was studied in anesthetized mongrel dogs with radioactive microspheres. In the early stages of shock, when carotid artery manipulation was avoided, outer cortical blood flow fell drastically and juxtamedullary flow was relatively well preserved. Carotid artery cannulation caused a redistribution of blood flow within the kidney even before hemorrhage, presumably by stimulating the carotid sinus reflex. Subsequently, with hemorrhage there was a parallel reduction in outer cortical and juxtamedullary blood flow.
138
Xe washout curves agreed with the microsphere findings. It was concluded that when the carotid artery was not disturbed, juxtamedullary blood flow was selectively preserved in the early stages of acute hypotensive hemorrhage.
Effects of Bradykinin and Autonomic Nervous System Inhibition on Systemic and Regional Hemodynamics in the Unanesthetized Rhesus Monkey
Authors: Reichgott Michael J. , Forsyth Ralph P. , Melmon Kenneth L.
Published: June 2012

Studies were performed in unanesthetized monkeys to determine if bradykinin infusions reproduce the circulatory events of early endotoxemia. Kinin infusions before and during autononiic ganglionic blockade with trimethaphan were significantly correlated (P <0.05) with decreases in mean arterial pressure. Kinin infusion at 15-18, µg/kg min
-
produced 26 mm Hg fall in mean blood pressure at 3 min, due to fall in total peripheral resistance of 14 mm Hg/liter min
-1
. Heart rate rose 23 beats/min. After 10 minutes of infusion, peripheral resistance had returned to base line, blood pressure remained low due to fall in cardiac output of 0.53 liters/min (P <0.01). Ganglionic blockade prevented recovery of resistance. Plasma bradykinin levels at 3 and 10 minutes were 14 and 15 µg/ml, respectively. Regional and systemic hemodynamic effects of kinin (15-18 µg/kg min were determined in 10 monkeys. After 10 minutes of infusion, bradykinin produced systemic effects. Regional flow measurement (by radioactive microsphere technique) demonstrated a pattern similar to that seen during hemorrhage. Canglionic blockade lowered mean arterial pressure 33 mm Hg by generalized vasodilatation, Kinin infusion then resulted in further vasodilatation and fall in blood pressure of 12 mm Hg, and cardiac output of 0.74 liters/min. Regional flow distribution during combined infusion was similar to that seen during early endotoxemia.
On Defining the Pulmonary Extravascular Water Volume
Authors: Brigham Kenneth L. , Ramsey Lloyd H. , Snell James D. , Merritt Cullen R.
Published: June 2012

To evaluate the effect of diffusion on the pulmonary extravascular water volume determined from indicator dilution studies, simultaneous comparisons of the pulmonary extravascular distribution volumes of tritiated water (THO) and of three lipid soluble substances with higher molecular weights were made. In 21 studies on pentobarbital-anesthetized dogs, the distribution volume of antipyrine (AP) was slightly smaller than that of THO (mean difference=2.86 ml±1.49 SE; 0.1<
P
<0.05). The results of 21 studies in conscious humans showed a slightly smaller distribution volume for
131
I-iodoantipyrine (IAP) than for THO (mean difference=15.62 ml±3.36 se;
P
>0.01). Neither the differences between THO and AP in dogs nor those between IAP and THO in humans correlated with either flow (τ=0.25 for dog studies; τ=0.07 for human studies) or the mean transit time of the intravascular indicator (τ=-0.17 for dog studies; τ=0.14 for human studies). No significant difference between the distribution volume of
14
C-ethanol(ETOH) and THO could be shown in either dogs (12 studies) or humans (15 studies). Relative lung-to-blood partitioning of IAP as compared to THO at equilibrium in dogs was 0.92±0.08; the same value for ETOH was 1.18±0.10. The findings strongly suggest that distribution volume for these indicators is independent of their diffusion characteristics and that IAP may be a reasonable substitute for THO in measuring pulmonary extravascular water volume.
Influence of Sodium and Potassium Content on Arterial Responsiveness
Authors: Burks Thomas F. , Spalding Charles T. , Jones Vernon D.
Published: June 2012

Vasoconstrictor responses to norepinephrine were determined during constant flow perfusion with warm Krebs solution in dog mesenteric arteries. The arteries were then stored 20-24 hours at 3°C in one of the following isosmotic solutions: Krebs, complex K (KC1, CaCl
2
, KHCO
3
and glucose), NaCl, KCl, sucrose, or mannitol. After storage, arteries were again perfused with warm Krebs solution, and vasoconstrictor responses to norepinephrine compared to prestorage control responses. Tissue levels of Na
+
and K
+
were determined before cold storage and after 0-35 minutes of poststorage perfusion with warm Krebs solution. Storage of arteries in mannitol or sucrose solution reduced their Na
+
and K
+
content, and during poststorage perfusion with warm Krebs solution their responsiveness gradually improved as they rapidly (within 5 minutes) regained Na
+
and slowly regained K
+
. Arteries stored in NaCl solution were initially more responsive than those stored in electrolyte- free solutions during poststorage perfusion with warm Krebs solution, and their responsiveness also improved as they regained K
+
. Arteries cold-stored in K
+
containing media (KCl and complex K solutions) quickly regained Na
+
, and their responsiveness exceeded prestorage values with 11 minutes of poststorage perfusion with warm Krebs solution. Since these data indicate that artery responsiveness may be related to tissue levels of both Na
+
+ and K
+
efforts were made to establish minimal levels of each ion required for "normal" responsiveness. The critical level of Na
+
appears to be approximately 30 µEq Na/g dry weight; the minimal effective K
+
content is apparently near 20 µEq K/g dry weight. If arteries contain at least minimal levels of K
+
and an excess (over 100 µEq/g) of Na
+
the magnitude of theft responses to vasoconstrictor stimuli is exaggerated
Effects of Body Surface Boundary and of Tissue Inhomogenelty on the Electrocardiogram of the Dog
Authors: Scher Allen M. , Ohm Winfried W. , Kerrick Wallace G. L. , Lewis Steven M. , Young Allan C.
Published: June 2012

The voltage-current relationship between intrathoracic ‘dipoles’ and body surface locations was examined in anesthetized dogs. Controlled currents were applied at body surface points, and potentials were recorded at the intrathoracic dipoles. A technique of fastening the electrodes to a cast made on the animal's torso permitted exact measurement of the torso and electrode geometry. The potentials recorded in the animal were compared with (1) an infinite-medium simulation performed on a digital computer, (2) a bounded- medium simulation performed in the plaster cast of each torso studied, and (3) a simulation involving a torso model containing heart and lungs. The correlation between recorded and simulated potentials was fair for the infinite-medium simulation, improved by the boundary, and further improved by the addition of inhomogeneity. Implications for electrocardiography are discussed.
Role of the Renin-Angiotensin System In the Pathogenesis of Severe Hypertension in Rats
Authors: Carretero O. A. , Kuk P. , Piwonska S. , Houle J. A. , Marin-Grez M.
Published: June 2012

Plasma renin levels are elevated in accelerated or malignant hypertension. To see if this increase of renin is a concurrent phenomenon or a pathogenetic factor in the increase of blood pressure, severe hypertension was produced in rats by occluding the aorta between the origins of the renal arteries. Eight days later, these animals had developed severe hypertension (mean blood pressure = 201 ± 3 mm Hg) and markedly elevated plasma renin levels (151 ± 35 ng angiotensin II/ml hr
-1
; normal range = 11 ± 0.6). When the kidney distal to the ligature was excised at the time of the coarctation, the animals developed only a moderate increase in blood pressure (mean = 120 ± 1.3 mm Hg) and their plasma renin levels remained in the normal range. When the nonnephrectomized animals with severe hypertension were injected with antibodies against angiotensin II, blood pressure decreased, reaching its lowest point (126 ± 12 mm Hg) 2 days later. This work demonstrates that the severe increase in blood pressure is not due to the mechanical increase in resistance caused by complete coarctation of the aorta; rather, it is due to a humoral factor produced by the kidney, and this factor is renin.
Changes in Forelimb Weight and Segmental Vascular Resistances Following Severe Hemorrhage
Authors: Grega George J. , Schwinghamer James M. , Haddy Francis J.
Published: June 2012

The forelimb was used to study capillary fluid fluxes following hemorrhage in dogs anesthetized with sodium pentobarbital. Arterial hemorrhage (48 ml/kg) and 4 hours of hypovolemia produced decreases in forelimb weight, arterial and venous pressures, and skin and skeletal muscle blood flows. Segmental resistances (large artery, small vessel, large vein) in both skin and skeletal muscle increased markedly, and the increase was either completely or largely maintained throughout the hypovolemic period. The large arteries and large veins constricted proportionately more than the small vessels following hemorrhage. In animals that survived the hypovolemic period, the large arteries and large veins constricted almost proportionately, whereas in the animals that died, the large veins constricted proportionately more than the large arteries. The weight loss exceeded forelimb vascular volume, indicating that net extravascular fluid reabsorption occurred. In fact, the weight loss from 60-240 minutes after hemorrhage began appears to be largely attributable to extravascular fluid reabsorption, since resistance and, inferentially, blood volume were relatively constant in the forelimb capacitance vessels. These data fail to support the hypothesis that fluid filtration is a determinant of irreversibility but rather suggest that the compensatory responses to blood loss in the forelimb, i.e., vasoconstriction and net extravascular fluid reabsorption, persist during severe prolonged hemorrhagic hypotension.
Centrally Mediated Effects of Cardiac Drugs: Strophanthin-K, Quinidine and Procaine Amide
Authors: WEINBERG S. J. , HALEY THOMAS J.
Published: June 2012

The extra-cardiac sites of action of strophanthin-K, quinidine and procaine amide have been investigated by injection of varying doses into the third ventricle of unanesthetized dogs. A profuse autonomic nervous system discharge was produced. Strophanthin-K produced a paroxysmal ventricular tachycardia resulting in death by ventricular fibrillation. Such effects could be blocked by prior intraventricular injection of either quinidine or procaine amide or by intravenous administration of hexamethonium.
A Method for Continuously Recording the Disappearance of Radioactive Tracers from Circulating Blood
Authors: MAcINTYRE WILLIAM J. , LEONARDS JACK R.
Published: June 2012

A method of continuous recording of the disappearance of radioactive materials from the circulating blood is described. By cannulation of the right femoral artery of dogs and leading the tubing past a scintillation counter into the right femoral vein a complete circuit is established in which the concentration of radioactivity may be continuously monitored. Curves showing concentration of the radioactive material versus time have been obtained following injection of iodinated (I
131
) plasma, Na
24
, I
131
, P
32
, K
42
, and colloidal Au
198
. No errors are introduced by sample withdrawal, timing of samples, or geometric variations.
Cholesterol Stimulation of Phosphatidyl Choline Formation
Authors: PILGERAM LAURENCE O. , GREENBERG DAVID M.
Published: June 2012

The conversion of ethanolamine to phosphatidyl choline was studied in liver slices from rats exposed to a high dietary intake of cholesterol in the presence of cholic acid. Cholesterol stimulated phosphatidyl choline formation per unit weight of liver tissue and increased the total liver mass thereby increasing further the total yield of phosphatidyl choline. These results are contrasted with the opposite effect of cholesterol on the liver phosphatides of the rabbit. A relationship between phosphatides and cholesterol metabolism and between species susceptibility to cholesterol induced atherosclerosis and phosphatide metabolism is pointed out.
The Effect of Epinephrine and Norepinephrine on Ventricular Vulnerability
Authors: HOFFMAN BRIAN F. , SIEBENS ARTHUR A. , CRANEFLELD PAUL F. , McC. BROOKS CHANDLER
Published: June 2012

The effectiveness of l-epinephrine and l-norepinephrine in enhancing ventricular vulnerability has been compared in twelve dogs by obtaining fibrillation thresholds for single test stimuli. Both agents produce similar increases in vulnerability immediately following injection, and similar decreases in vulnerability at longer intervals following drug administration. These changes in vulnerability occur simultaneously with alterations of the same direction in resting excitability, and are dose-related. It is concluded that these agents have qualitatively and quantitatively similar effects on ventricular vulnerability.
Effects of Acute and Chronic Digoxin Administration in Dogs with Right-Sided Congestive Heart Failure Produced by Pulmonary Artery Constriction
Authors: DAVIS JAMES O. , HOWELL DAVID S. , HYATT ROBERT E. , CASPEU ALFKED
Published: June 2012

Acute and chronic responses to digoxin have been studied in dogs with cardiac failure secondary to constriction of the pulmonary artery. Cardiovascular and renal hemodynamic function improved and, frequently, a striking increase in sodium (Na) excretion resulted. The data suggest a direct myocardial action of digoxin and provide evidence of impaired myocardial function similar to that observed in patients with congestive heart failure.
Thrombocytogenesis in Surgical Patients
Authors: WILLIAMS JOHN A. , BELKO JOHN S. , WARREN RICHAHD
Published: June 2012

Comparative studies of peripheral blood and bone marrow have shown that the postoperative marked and sustained reduction of blood platelets is accompanied by a block in the mechanism of delivery of platelets into the blood stream and a delay in maturation of blast cells of the megakaryocyte lineage.
Tissue Permeability--a Factor in Atherogenesis
Authors: WANG CHUN-I , SCHAEFER LOUIS E. , ADLERSBERG DAVID
Published: June 2012

Cortisone has a retarding effect on atherogenesis in cholesterol-fed rabbits, despite higher plasma cholesterol levels. This effect of cortisone is prevented by administration of hyaluronidase. The latter intensifies atherosclerosis and deposition of cholesterol in the liver.
Lipids of the Serum and Connective Tissue of the Rat and Rabbit
Authors: NOBLE NANCY L. , BOUCEK ROBERT J.
Published: June 2012

The lipicl profile of connective tissue, isolated from the rat and the rabbit, by the sponge-implantation technique, is presented. This tissue is rich in cholesterol, phospholipid, and neutral fat. Several sex, age, and species differences in the concentration of its lipids are reported. Simultaneous determination of serum lipids indicates that there is no significant correlation between the lipid values of the serum and connective tissue. The relationship of these findings in connective tissue, the chief constituent of the intima, to the problem of atherosclerosis is discussed.
Effects of Protoveratrine, Serotonin and ATP on Afferent and Splanchnic Nerve Activity
Authors: DONTAS A. S.
Published: June 2012

Splanchnic outflow was studied along with carotid and aortic presso- and chemoreceptor inflow in cats under a variety of conditions. Splanchnic activity was increased by a decrease in presso- or increase in chemoreceptor activity and vice-versa. Blood pressure rose following splanchnic activation. Protoveratrine and serotonin, reported to activate the "coronary chemoreflex," depressed completely splanchnic outflow, without enhancing pressoreceptor activity. Prolonged hypotension from protoveratrine coincided with partial return of splanchnic activity and tonic discharge of pressoreceptors. ATP increased splanchnic activity simultaneously with the hypotension and it is suggested that it be excluded from the list of drugs eliciting the "coronary chemoreflex."
A Study of Hypotension (Shock) Produced by Meningococcus Toxin
Authors: EBERT RICHARD V. , BORDEN CRAIG W. , HALL WENDELL H. , GOLD DAVID
Published: June 2012

Hemodynamic alterations were produced in dogs by injecting meningococcus toxin. Hypotension and a decrease in cardiac output occurred without significant reduction in blood volume. These changes were accentuated by small hemorrhage. Increasing the blood volume above normal led to marked increase in cardiac output with slight increase in arterial pressure. The arterial pressure was markedly increased by the administration of levarterenol but large doses were required. Cortisone did not modify the effect of meningococcus toxin on the circulation. Meningococcus toxin apparently produced its effect by increasing the volume of blood in small blood vessels.
Influence of Antiarrhythmic Agents on Calcium-Induced Cardiac Arrhythmias in the Rat
Authors: WINBURY MARTIN M. , HEMMER MIRIAM L.
Published: June 2012

The effect of quinidine, procaine amide and five new antiarrhythmic compounds on calcium-induced arrhythmias in the rat are described. When the compounds prevented fibrillation, the other actions of calcium on cardiac rhythm were revealed.
Energy Sources for Contraction of the Rat Ventricle in Phosphate Media
Authors: BERMAN DAVID A. , SAUNDERS PAUL R.
Published: June 2012

Various substrates were tested for their ability to restore the amplitude of contraction of hypodynamic electrically-stimulated rat ventricle strips suspended in a phosphate-buffered medium. Greatest recovery of the contractile activity was obtained with pyruvate; lactate, β-hydroxybutyrate and acetate were more effective than succinate and glucose. The finding that glucose, in contrast to pyruvate, was relatively ineffective as an energy source for contraction, when a phosphate-buffered medium was employed, suggests that the defect was due to a rate-limiting step in the conversion of glucose to pyruvate, rather than to an impairment in the functioning of the Krebs cycle.
The Use of Indigo Carmine for Dye Dilution Curves
Authors: LACY WILLIAM W. , UGAZ CARLOS , NEWMAN ELLIOT V. , Arnold Thomas G. , Ramsey Lloyd H.
Published: June 2012

Investigation of the properties of indigo carmine reveals that it may be more suitable than the dye, T-1824, for circulatory studies that are now commonly carried out using the dye dilution principle of Stewart and Hamilton. Comparison is made of simultaneous dilution curves of indigo carmine and radioactive iodinated serum albumin. Apparently, indigo carmine is bound to protein firmly enough to remain the plasma in one passage through the heart and lungs, but not too firmly to be extracted rapidly from the plasma by excretory systems in the kidney and liver. This allows repeated injections without accumulation.
Electrolytes and pH Changes in Relation to Hypothermic Ventricular Fibrillation
Authors: COVINO BENJAMIN G. , HEGNAUER A. H.
Published: June 2012

Coronary arteriovenous electrolyte differences were studied in normo- and hypercapneic dogs at normal temperature and at 24 C. The ions measured were sodium, potassium, calcium, magnesium, chloride and hydrogen. Coronary arteriovenous electrolyte differences did not change during cooling in 16 dogs which did not suffer ventricular fibrillation. Ten hypercapneic hypothermia dogs exhibited characteristic Ca, K, and H ion changes at 24 C. before succumbing to ventricular fibrillation. The data suggest that ventricular fibrillation at low body temperatures is related to a gain of Ca and a loss of K and H ions by the hypothermia hypercapneic myocardium.
Length-Circumference Relations of the Left Ventricle
Authors: RUSHMER ROBERT F. , Nash Alden A. , Franklin Dean L. , Crystal Dean K. , Lobb Allan W. , Wagner Clyde
Published: June 2012

Changes in length and circumference of the left ventricle were recorded simultaneously by variable resistance gages on its external surface in intact dogs. The absolute changes in circumference were considerably greater than the changes in length, but the relative changes in these dimensions were similar (averaging around 2 to 3 per cent). Under most circumstances, the length and circumference vary in the same direction but occasionally inexplicable differences in response were observed.
Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog
Authors: BAILEY JOHN C. , GREENSPAN KALMAN , ELIZARI MARCELO V. , ANDERSON GARY J. , FISCH CHARLES
Published: June 2012

Conventional intracellular recordings from the bundle of His and right bundle branch of the canine heart demonstrated that the slope of diastolic depolarization is markedly depressed by superfusion with relatively small concentrations (4-8 µg/ml) of acetylcholine. As the cells become less automatic, take-off potential increases, rise time of phase 0 is reduced, action potential amplitude increases, and conduction proceeds more rapidly.
Complement-Mediated Vasoconstriction and Graft Rejection
Authors: JENSEN JOERG A. , DAVIES DANA , LINN BERNARD S. , SNYDERMAN RALPH , FRANKLIN LINDA
Published: June 2012

The hyperacute rejection of renal allografts has much in common with pig-to-dog renal xenograft rejections. An analysis of the xenograft model revealed new functional aspects of graft rejection that appear to be an integral part of the humoral immune injury. Anaphylatoxin or C5a, a cleavage product of the fifth complement component was shown to play a major role in the rejection of isolated kidneys; it was generated in pig and dog serum by activation of the complement system and caused severe Vasoconstriction in the renal vasculature. It is suggested that histocompatibility antibodies and complement may affect allograft survival via this potent mediator.