bluuebunny/crossref_metadata_2025 huggingface dataset:
Potassium in Dog Ventricular Muscle: Kinetic Studies of Distribution and Effects of Varying Frequency of Contraction and Potassium Concentration of Perfusate
Authors: Langer G. A. , Brady A. J. , Serena S.D. , Ton S.T.
Published: June 2012

Four phases (0 to 3) were defined kinetically for potassium in the dog papillary muscle when perfused arterially for four to five hours with solution containing 4 mM/liter K
+
. Total tissue K
+
fell from 91.1±1.99 to 41.0±1.06 mmoles/liter after three hours perfusion. It then remained stable during the period when kinetic studies were done. The mean rate constant λ (min
-1
), potassium content (mmoles/liter tissue water) and suggested origin of each phase are respectively: (phase 0) λ
0
= 3.2, 0.3, vascular; (phase 1) λ
1
= 0.65, 2.06, interstitial; (phase 2) λ
2
= 0.0139, 39.3, intracellular; (phase 3) λ
3
< 0.004, <0.5, origin unknown.

Alteration of K
+
concentration in perfusing fluid produced significant changes in the intracellular exchange rate of K
+
. This was in marked contrast to increments in frequency of contraction which had no effect on the overall exchangeability of intracellular potassium. Increases in rate, however, were associated with a transient net loss of intracellular K
+
. This loss continued if the active tension of the muscle declined and if contracture progressed. The loss ceased if muscle function remained stable during continued increased frequency of contraction. A positive tension staircase was approximately proportional to the net K
+
loss. The net K
+
loss was 0.93 mmole/liter tissue water in nine muscles in which a mean 27 beats/min rate increment was introduced for a mean of 16 minutes. This represented 2.4% of intracellular K
+
.

A significant time lag was found before the net K
+
loss reached a maximum rate and began to decline. This is compared with the previously demonstrated transient net increment in Ca
++
uptake that accompanies increased frequency of contraction. These ionic movements are consistent with the theory that Na
+
movements in and out of a "specialized membrane region" are related to Ca
++
movements and thereby influence the control of myocardial contractility.
Cystine Deficiency and Cholesterol Metabolism in Primates
Authors: Mann George V.
Published: June 2012

Cebus
and
Rhesus
monkeys suppress the in vivo production of cholesterol when fed cholesterol. This suppression is less than that observed in rats and it did not occur in
Lagothrix
monkeys.
Cebus
monkeys deficient in cystine lose their efficiency in removing cholesterol when the body pool is large. One result is an elevation of the plasma level of cholesterol.
Influence of Various Dietary Fats on Hypercholesterolemia and Atherogenesis in Cockerels
Authors: Clarke Gregory B. , Jain Savitri , Pick Ruth , Katz Louis N. , Johnson P. , Kakita C.
Published: June 2012

When cockerels were given a cholesterol supplemented, fat-free, semi-synthetic diet as the basic ration, all oils and solid fats were atherogenic and caused elevated serum cholesterol levels. The degree of hypercholesterolemia and atherogenesis was related to fatty acid composition of the fat fed. Margarines were less atherogenic and less hypercholesterolemic than oils. The additives used in the preparation of margarine have some influence on maintaining lower cholesterol levels, but do not appear to have any significant effects on atherogenesis. The structural isomers formed during margarine manufacture may be responsible through an alteration of lipid metabolism.
Ventricular Conduction and Refractoriness During Hypothermia
Authors: Torres Joseph C. , Warschaw Rachelle , Chase Patricia
Published: June 2012

The effect of hypothermia on ventricular conduction was determined with a multi-terminal electrode sutured to the epicardial surface. Measurements of conduction intervals revealed average increases of 95% at 22°C in 13 dogs and 148% at 20°C in seven dogs that survived to this temperature. The mean conduction velocity estimated at 0.55 m/sec at 37°C diminished to 0.29 m/sec and 0.19 m/sec respectively at 22° and 20°C. An apparent overall exponential relationship between conduction velocity and temperature was observed, although below 30°C the rate of conduction decreased almost linearly with a Q
10
, of 1.6 to 1.8.

Individual measurements along both rows of intersecting electrode terminals revealed slightly different rates of conduction. However, within the entire group the direction of relatively faster conduction was inconsistent and, furthermore, the changes of conduction velocity with hypothermia were practically identical for the two recording alignments in all instances.

During cooling to 22°C the absolute and the relative phases of ventricular refractoriness both increased by more than 200% of the control values observed at 37°C. This threefold effect on recovery of excitability was in contrast to the twofold slowing of conduction at the same temperature.

It is concluded that the occurrence of ventricular fibrillation during hypothermia cannot be explained adequately by assuming a greater slowing of conduction relative to prolongation of refractoriness.
Potentiation of Myocardial Contractility by Continual Premature Extra-activations
Authors: Koch-Weser Jan
Published: June 2012

Introduction of a premature activation into each interval between regular contractions of isolated kitten papillary muscles greatly increases isometric tension development. This premature extra-activation potentiation is a manifestation of the interval-strength relationship of ventricular myocardium and results both from the increase in the overall frequency of activation (frequency potentiation) and from the prematurity of the extra-activations (prematurity potentiation).

A premature electrical stimulus which elicits a propagated action potential is always followed by a mechanically apparent activation of the contractile element. Potentiation of the regular contractions follows from the occurrence of premature, propagated action potentials, and/or the resulting activation processes. It does not depend on the extent to which the contractile element can respond to the premature activation.

Prematurity potentiation results solely from an increase in the degree of activation of the contractile element. It increases over a wide range with the prematurity of the extra-activation but always decreases when the prematurity interval approaches the refractory period closely. The extent of prematurity potentiation varies with the basal frequency of contraction; it tends to raise tension development to the same high level whatever the basal frequency. Although nonpotentiated strength of contraction increases greatly with frequency, potentiated contractions at low frequencies are stronger than nonpotentiated contractions at high frequencies.

At normal temperature summation of contractions plays no role in prematurity potentiation. Similarly, release of endogenous norepinephrine is not involved, but such release does occur and interferes with the study of potentiation when high-intensity stimuli are used. Premature activations may transiently alter the concentration of available Ca
++
in an intracellular site critical for activation of the contractile element.
Determinants of Thyroxine-Induced Cardiac Hypertrophy in Mice
Authors: Cohen Jules , Aroesty Julian M. , Rosenfeld Michael G.
Published: June 2012

Thyroxine was administered to mice to determine whether the cardiac hypertrophy which accompanies experimental thyrotoxicosis is a result of circulatory changes produced by thyroxine, or the result of a hormonal effect on myocardial growth.

When mice were fed both reserpine and thyroxine they developed as much cardiac hypertrophy as those fed thyroxine alone, although the circulatory changes associated with thyrotoxicosis were greatly reduced by reserpine treatment. In addition, when mice were injected with synthetic
l
-thyroxine, the rate of cardiac protein synthesis was increased before any definite circulatory changes were observed.

The results suggest an effect of thyroid hormone on cardiac protein synthesis that is independent of the effects of the hormone on the general circulation.
Applications of the Lagged Normal Density Curve as a Model for Arterial Dilution Curves
Authors: Bassingthwaighte James B. , Ackerman Francis H. , Wood Earl H.
Published: June 2012

1. Indicator dilution curves (concentration versus time) were recorded from the femoral and dorsalis pedis arteries of normal men after injections of indocyanine green into the superior vena cava or thoracic aorta. A four-parameter mathematical model, the lagged normal density curve, adequately described the form of the portion of these curves representing indicator passing by the sampling site for the first time.

2. The curves were observed to be of constant shape, the spread of the curve being approximately linearly related to the mean transit time t. The spread was dependent on the injection site; dispersion was shown to be greatest in the central circulation, less in the aorta, and still less in the arteries of the leg. For the latter segment, the mean transit time t. The spread was dependent 0.3 t, the square root of the variance was 0.18 t, and the parameters of the lagged normal density curve, σ and τ, were 0.09 t and 0.16 t, respectively.

3. The linear relationships between parameters of the recorded curves and the mean transit times indicate that the effect of rate of flow, over a range from resting values to four to six times above resting values, has almost no influence on the dispersion. This suggests that the flow characteristics are essentially unchanged over this range. Such linear relationships always occur with laminar flow but cannot prove its existence because turbulent flow can also produce this result. The similarity of the linear relationships at low flow rates to those at high flow rates, where turbulence almost certainly is present, suggests that arterial flow is usually turbulent. Turbulence may be expected at relatively low flow rates in nonhomogeneous fluids driven by a pulsatile head of pressure through elastic, branched, tapering, curved tubes.
Non-Respiratory Oscillations in Systemic Arterial Pressure of Dogs
Authors: Race David , Rosenbaum Maurice
Published: June 2012

In dogs the condition of the cardiovascular control system was investigated quantitatively during haemorrhage, by using a system of transient inputs and by recording arterial blood pressure. The analysis of our results using standard control system techniques demonstrates a probable increase in open loop gain and a reduction of natural frequency. The implications of these findings are discussed.
Effect of Afterload on Force-Velocity Relations and Contractile Element Work in the Intact Dog Heart
Authors: Levine Herbert J. , Forwand Stanley A. , Mclntyre Kevin M. , Schechter Eliot
Published: June 2012

The effects of heightened afterload on force-velocity relations and on contractile element work of single systoles were examined in the intact dog heart. The force-velocity curve described during the course of a normal systole represents a composite of curves, each with its own projected isometric force determined by instantaneous changes in fiber length. During the first systole following an afterload intervention, reciprocal changes in force and velocity were observed together with an extension of the projected isometric-force.

The effect of afterload on contractile element work was determined by: (1) the direction and magnitude of the afterload, and (2) the afterload of the control beat itself. When the control beat was lightly loaded, an increase in afterload increased contractile element work by two additive mechanisms: (1) an increase in mean isometric force, and (2) a shift of force-velocity relations to positions of greater power and work production. In normally loaded control beats, an increase in afterload resulted in a decrease in contractile element work, despite the fact that mean isometric force was increased. In this instance, force-velocity relations were shifted to positions where less power and work could be achieved. Thus, the normal systole appears to function at the apex of the contractile element work-load curve (near 60% of the isometric load).

Evidence is presented which suggests that the apparent maximum active state of the entire left ventricle is generally achieved within 30 to 50 msec after the onset of pressure rise, and that its decay is accompanied by abrupt divergence of the force-velocity relations from the inverse curve of that beat. A sudden increase in afterload does not appear to influence the duration of the maximum active state, although the duration of positive contractile element work is shortened and that of negative contractile element work prolonged.
Production of Renin by Human Juxtaglomerular Cells in Vitro
Authors: ROBERTSON ABEL L. , SMEBY ROBERT R. , BUMPUS F. MERLIN , PAGE IRVINE H.
Published: June 2012

New organ culture methods permit growth of human renal cortical cells fulfilling all known criteria of juxtaglomerular cells. Two types of granules were observed with the electron microscope. These granules showed an increase in size and number during the growth of these cultures. Their presence in cells was demonstrated by Bowie's, basic fuchsin-crystal violet, and fluorochrome staining methods. Puromycin or actinomycin D caused a reduction in the number of cytoplasmic granules, while 1% oxygen in the gas phase of the culture caused an increase. Specific reaction of these granules with rabbit antihuman renin antibody was demonstrated. Other cellular structures did not react with this antibody. Similar granules were observed in the media of hyperplastic, interlobular arterioles but not in normal arterioles or arterioles of other vascular beds. Bundles of myofilaments could be observed between the cytoplasmic granules in cultured cells. Bioassays of renin activity of the supernatant culture medium showed that it contained renin if granulated cells were present in the culture. All juxtaglomerular cells in culture produced granules, but only those cells which grew from kidneys with pathological changes released renin, suggesting that the stimulus for renin release existed in the intact kidney. This stimulus for renin release seemed to be rapidly lost during culture growth.
Role of Chemicals in Local Regulation of Vascular Resistance
Authors: HADDY FRANCIS J.
Published: June 2012

Changes in flow and metabolism influence vascular resistance in part through alteration of the concentration of vasoactive chemicals. Among the chemicals which may have a role in this local regulation are oxygen, hydrogen, potassium, magnesium, adenosine, AMP, ADP, ATP, and the Krebs intermediate metabolites. It is likely that several chemicals operate simultaneously, and possibly the dominant chemical is not the same in every organ.
Circulatory Responses to Norepinephrine After Prolonged Treatment with Chlorothiazide
Authors: ECKSTEIN JOHN W. , WENDLING MICHAEL G. , ABBOUD FRANCOIS M.
Published: June 2012

Cardiovascular responses to graded intravenous infusions of norepinephrine were measured in untreated control dogs and in dogs treated for five weeks with oral chlorothiazide. Observations were made both before and after administration of a ganglionic blocking agent. In these experiments, chlorothiazide reduced the responses of the peripheral blood vessels to the vasoconstrictor effect of norepinephrine. This effect was apparent both before and after ganglionic blockade, suggesting that modification of resting neurogenic vasomotor tone did not play a major role in the reduced responsiveness. Cardiac output and heart rate were greater during norepinephrine infusion in treated dogs before hexamethonium. Output and rate became similar in both treated and untreated groups after hexamethonium. The results provide additional evidence to support the hypothesis that chlorothiazide reduces the effectiveness of cardioinhibitory reflexes.
Medullary Control of Vascular Resistance
Authors: AAKI VINCENT S. , BRODY MICHAEL J.
Published: June 2012

Relationships between electrical activity in medullary vasomotor areas and reflex changes in peripheral vascular resistance were studied in dogs in which the hindquarters were autoperfused. Electrical stimulation through bipolar electrodes indicated a diffuse distribution of vasoactive points. Points yielding vasoconstrictor responses were found primarily in the rostral half of the medulla oblongata, while vasodilator points were located in the caudal and ventral portions of the medulla. Extensive crossing of vasomotor pathways was shown by the fact that stimulation of a single medullary point resulted in vascular resistance changes in both the ipsilateral and contralateral limbs. Stimulation of vasodilator points resulted in noncholinergic active vasodilatation in the hindlimb. The dilatation was considered to be active because it exceeded the sustained dilatation produced by lumbar sympathectomy and was reduced in magnitude by the antihistamine, ripelennamine. Discharge recorded through the electrodes from the same points which, when stimulated, gave vasomotor responses in the limb was larger in the vasoconstrictor point than in the vasodilator point. This difference may represent a central reflection of tonic sympathetic vasoconstrictor discharge. Reflex vasodilatation produced by intravenous norepinephrine was accompanied by a small but significant increase in activity recorded from vasodilator points. Other reflex stimuli, which included asphyxia and elevation and depression of carotid sinus pressure, elicited changes in electrical activity from the vasoconstrictor and vasodilator areas which, although small in magnitude, followed directions which were predicted on the basis of the existence of separate vasodilator and vasoconstrictor neurone pools. It was concluded that neurones exist in the medulla which probably play a role in exciting vasodilator pathways involved in reflex vasodilatation.
Simultaneous Pressure, Flow and Diameter of the Vena Cava with Fright and Exercise
Authors: TAFUR EMILIO , GUNTHEROTH WARREN G. , Breozeale Donald G. , McGough George A.
Published: June 2012

The diameter, distending pressure and flow in the superior vena cava and aortic flow were recorded simultaneously in unanesthetized dogs. Atrial systole produced a regurgitant flow pulse and an increase in pressure and diameter. Ventricular systole produced a sharp decrease in caval diameter and a large increase in flow. A second flow pulse occurred during ventricular diastole. Inspiration accelerated flow in the cava. During exercise, the caval diameter invariably decreased. Venoconstriction, however, could be unequivocally demonstrated in only 26% of the treadmill runs. In 88% of 33 recorded treadmill runs, the flow in the vena cava increased before the heart rate increased which, in turn, preceded the increase in aortic stroke volume. Frightening the animal produced a prompt decrease in caval diameter and distending pressure; this gave way to increased pressure, but without a corresponding increase in diameter. Epinephrine and norepinephrine produced a sustained increase in distending pressure and an initial decrease and a more sustained increase in diameter. Isoproterenol produced tachycardia and a decrease in distending pressure and diameter. Acetylcholine caused an initial bradycardia which was associated with an increase in diameter and pressure in the vena cava followed quickly by prolonged tachycardia which was associated with a decrease in pressure and diameter.
Pressure-Flow Relations in Dog Arteries
Authors: ATTINGER E. O. , SUGAWARA H. , NAVARRO A. , RICCETTO A. , MARTIN R.
Published: June 2012

The propagation of the arterial pressure and flow pulses through the vascular beds is characterized by marked changes in shape and magnitude. In order to understand better the mechanisms which account for these changes, instantaneous pressures and flows were measured simultaneously at various sites in the arterial tree of 12 anesthetized dogs, using Statham strain gauges and electromagnetic flowmeters. The data were processed by on-line Fourier analysis and the frequency spectra of pressure, flow and vascular impedance at these sites were evaluated. In these dogs about 10% of the cardiac output was distributed to the head, 14% to the kidney, 35% to the gastrointestinal tract, 14% to the pelvic organs and 6% to the legs. The input impedances of the various beds were frequency dependent, the frequency-dependent components varying between 2 and 45% of the corresponding D-C impedances (peripheral vascular resistance). The viscous losses associated with pulsatile flow were larger than those for corresponding steady flows. The excess losses varied between 9 and 30% of the mean flow losses. The marked decrease in cross section down the aorta lead to considerable acceleration of the mean blood velocity and corresponding pressure losses despite the drainage through aortic branches. Comparisons of measured flows with those predicted from Womersley's theory showed satisfactory agreement for short vascular segments. However the theory underestimates the losses occurring in the nonuniform arterial tree. On the basis of anatomic measurements, the space dependence of resistance, inertance and vascular distensibility was evaluated.
Lipid and Carbohydrate Metabolism of Myocardium During the Biphasic Inotropic Response to Epinephrine
Authors: REGAN TIMOTHY J. , MOSCHOS CHRISTOS B. , LEHAN PATRICK H. , OLDEWURTEL HENRY A. , HELLEMS HARPER K.
Published: June 2012

The metabolic response of the left ventricle to a 90 min regional infusion of 1-epinephrine (5 µg/min) was assessed in the intact anesthetized dog for 3 hr. The first hour was characterized by a rise in stroke output at constant filling pressure. Subsequently, contractility fell and there was release of K and PO
4
ions as well as SGOT from the myocardium that was attributed to tissue injury. The myocardial RQ rose for the first hour, presumably due to glycogenolysis, since carbohydrate extraction from blood was unaltered. Production of lactate by the myocardium during the RQ rise occurred without ischemia, since blood flow (Kr
85
method) and O
2
uptake rose 10%. The proportionately greater increase in contractility was not consistent with "O
2
wasting" as a basis for the injury. After 1 hr the RQ fell to levels consistent with predominant lipid utilization. However, FFA extraction declined and the oxidation, extraction and incorporation of palmitate-l-C
14
into tissue lipid were diminished during hormone exhibition. Plasma triglyceride uptake, insignificant in controls, was enhanced during the 3 hr without a rise in arterial concentration. Oxidation of this lipid was insufficient to prevent a threefold triglyceride increment in the myocardium. The authors discuss a possible relationship of these metabolic alterations to the pathophysiologic response induced by epinephrine.
Cardiac Norepinephrine Stores and the Contractile State of Heart Muscle
Authors: SPANN JAMES F. , SONNENBLICK EDMUND H. , COOPER THEODORE , CHIDSEY CHARLES A. , WILLMAN VALLEE L. , BRAUNWALD EUGENE
Published: June 2012

In order to assess the role played by endogenous norepinephrine (NE) stores in the intrinsic contractile state of cardiac muscle, the right ventricular papillary muscles from normal cats and cats with cardiac NE depletion produced by chronic cardiac denervation or reserpine pretreatment were studied. The contractile state of NE-depleted ventricular myocardium was found to be normal. The resting and active length-tension curves, the forcevelocity relations, and the augmentation of isometric tension achieved by paired electrical stimulation and by increasing frequency of contraction were not depressed in either group of NE-depleted muscles. Similarly, no changes in the absolute refractory period and electrical excitability were observed. It is concluded that cardiac stores of NE are not fundamental for maintaining the intrinsic contractile state of the myocardium. Further, release of endogenous NE from cardiac muscle does not appear to play an essential role in the mediation of the positive inotropic effects of increasing frequency of contraction or of sustained postextrasystolic potentiation.
Collagen and Elastin Content in Canine Arteries Selected from Functionally Different Vascular Beds
Authors: FISCHER GRACE M. , LLAURADO JOSEP G.
Published: June 2012

The amount of collagen and elastin in normal canine arteries was determined biochemically in nine different sites. The total collagen and elastin ranges from 58 to 75% of the weight of the dry defatted artery. Reasons are adduced to propose that the expression of results as the ratio of collagen to elastin (C/E) is a useful index of the relative distensibility for the maintenance tension of arterial wall. Two arteries, carotid and renal, which are pathways to blood pressure sensors, have a statistically significantly higher C/E than the femoral and mesenteric arteries, which are pathways to regulated beds. The highest C/E was found in the coronary artery. Results are interpreted in relation to the function of the vascular beds to which the representative arterial specimens belong.
Interstitial Fluid Pressure: III. Its Effect on Resistance to Tissue Fluid Mobility
Authors: GUYTON ARTHUR C. , SCHEEL KONRAD , MURPHREE DENNIS
Published: June 2012

The resistance to fluid mobility in the interstitial fluid spaces has been measured between perforated catheters inserted into the subcutaneous abdominal tissues of the dog and between perforated capsules implanted in the tissues 1 month previously. When the pressures in the catheters or perforated capsules were less than atmospheric pressure, the resistance to fluid movement was almost infinite, but when the pressures were increased almost to or above atmospheric pressure the resistance usually decreased more than 100,000-fold, indicating a suddenly increased size of the tissue spaces.

The shape of the pressure-volume curve relating (a) interstitial fluid pressure to (b) volume of
mobile
interstitial fluid was calculated from pressure-conductance curves recorded in these experiments. On comparing this pressure-volume curve with a previously measured pressure-volume curve of the entire interstitial fluid compartment, two important points were observed: first, both curves exhibit a sudden increase in volume when the interstitial fluid pressure rises above atmospheric pressure. Second, the mobile interstitial fluid volume approaches zero when the interstitial fluid pressure falls below atmospheric pressure while the measured volume is still very great. It is postulated that this difference is caused by entrapment of large amounts of water in a relatively immobile state in the gelatinous matrix of the ground substance filling the interstitial spaces.
Elastic Environment of the Capillary Bed
Authors: FUNG Y. C. , ZWEIFACH BENJAMIN W. , INTAGLIETTA MARCOS
Published: June 2012

To determine the degree to which the capillary blood vessels in vivo are supported by the elasticity of the surrounding tissue, a study was made of the elastic properties of the mesentery of the rabbit. A torsion test was made on a circular membrane of the avascular region of the mesentery, by applying a graded static torque and measuring the resulting deformation. The mesentery was found to have a modulus of rigidity in the same category as that of larger arteries and veins. It has a nonlinear stress-strain relationship with a tendency to harden at larger strains. In torsion experiments, the shear modulus G can be reduced to the following form

G = µ+c
2
|τ|

Where c
2
is a constant and |τ| is the absolute value of the shear stress. The constant µ depends on the initial tension in the membrane. For the mesentery specimens, µ ranges from 215 to 1900 gm/cm
2
, whereas the nondimensional constant c
2
has an average value of 8.23 with a standard deviation of 2.1.

The hypothesis is advanced that the medium in which the capillaries of the mesentery are embedded is a gel and the capillary in effect is a tunnel in this gel. Such a hypothesis could explain the apparent rigidity of the blood capillaries.
Relation of Variations in Activation Order to Intraventricular Pressures during Premature Beats
Authors: MILLAR KAY , EICH ROBERT H. , ABILDSKOV J. A.
Published: June 2012

A comprehensive study on open chest anesthetized dogs was done to investigate the influence of intraventricular activation order on cardiac performance and to evaluate the degree to which entry into the conduction system might contribute to the synchrony of contraction in the ventricle opposite the stimulus site. Intraventricular pressures were measured during premature beats from several ventricular sites and over the entire range of the cardiac cycle. For each site, intraventricular pressures during the premature beats were plotted vs. time of delivery of the stimulus and also vs. time of onset of pressure rise in the ventricle being considered. The prior observation that higher ventricular pressures occur during premature beats initiated in the opposite ventricle was confirmed. Evidence is presented that the major factor responsible is the increased filling and recovery interval permitted by the conduction time of the activation front arriving from the opposite ventricle. After correction for filling and recovery time, there were still differences due to site of origin of the premature beat, with those delivered to the apex resulting in the highest left ventricular pressures. The hypothesis that a more synchronous contraction results from stimulation of sites on the contralateral, rather than the ipsilateral ventricle, was not substantiated.
Relationship between Body Surface Potential and Ventricular Excitation in the Dog
Authors: BOINEAU JOHN P. , SPACH MADISON S. , PILKINGTON THEO C. , BARR ROGER C.
Published: June 2012

The distribution of body surface potential was studied in normal dogs by time normalization of nonsimuitaneously recorded voltages from 200 thoracic electrocardiograms using a digital computer technique. In addition, ventricular excitation data were obtained in the same animals using Scher myo-cardial plunge electrodes. Subsequently, the external surface voltage distribution was correlated spatially and temporally with the process of ventricular activation. It was noted that "dipolar" and "nondipolar" surface voltage patterns were related to the configuration of the instantaneous activation distribution in the ventricles. The reproducibility of the data obtained from the body surface and within the ventricles, and the observed consistent correlations between these two events indicate that there is a predictable relationship between major "inside-outside" activities.
Renal Angiotensinase Activity
Authors: ITSKOVITZ HAROLD D. , MILLER LEONARD D.
Published: June 2012

A rat bioassay technique was employed to determine the localization and properties of the angiotensinase activity present in kidney homogenates of anesthetized rats. The angiotensinase activity per gram of renal cortex was four times greater than renal papilla or medulla. The complete destruction of proximal renal tubular cells by mercuric chloride resulted in losses of cortical angiotensinase activity averaging 40% of control values. The destruction of cells of both the proximal and distal renal tubules by sodium potassium tartrate caused a 90% reduction in angiotensinase activity. Marked reductions in cortical angiotensinase activity were measured in rats injected with meralluride 2 hours previously. The addition of meralluride to in vitro systems of normal rat kidney homogenates caused similar depressions of angiotensinase activity. The presence of reduced glutathione in the reaction media interfered with the ability of meralluride to inhibit angiotensinase and enhanced the activity of this enzyme to greater than normal levels in the absence of the mercurial. Ammonium ion in a concentration of.18 m inhibited angiotensinase activity of renal cortical homogenates by a moderate degree. When both meralluride and ammonium were present in the homogenate system their effects to depress angiotensinase appeared additive.
Effect of Cycle-Length Alteration upon the Configuration of the Canine Ventricular Action Potential
Authors: EDMONDS ROBERT E. , GREENSPAN KALMAN , FISCH CHARLES
Published: June 2012

Action potentials recorded from canine ventricular fibers displayed characteristic alterations in configuration upon abrupt change in the cycle length. After a relative prolongation of the diastolic interval, abbreviation of phase 2 and slowing of phase 3 were consistently observed, while a relative shortening of diastole was terminated by an action potential displaying prolongation of phase 2 and a steeper phase 3. Neither circumstance was attended by a consistent alteration in action potential duration. The more conventional view, directly relating duration of phase 2 to the length of the preceding diastole, clearly does not obtain immediately following an abrupt alteration of cycle length.

This cycle-length-dependent phenomenon may account, in part, for the post-extrasystolic T-wave alterations observed in the human electrocardiogram. It is also consistent with the clinical observation that such T-wave changes may occur without premature contractions, requiring only a relative prolongation of the R-R interval. Evidence is also presented which relates electrical alter-nans of the T wave to this interval-dependent phenomenon.

This characteristic change in action potential configuration occurs under the same temporal circumstances that others have associated with potentiation of contractility. It is therefore suggested that these inotropic phenomena and changes in action potential configuration may relate to alterations in membrane permeability.
Functional Distribution of the Peripheral Cardiac Sympathetic Pathways
Authors: LEVY MATTHEW N. , NG MANUEL L. , ZIESKE HARRISON , Nelson Geraldine
Published: June 2012

The functional peripheral cardiac sympathetic pathways of the dog were delineated in isovolumetric left ventricle preparations. In unpaced hearts, supramaximal stimuli at 2 cycles/sec to the right stellate ganglion caused the heart rate to increase 2.8 times more than stimuli applied to the left side. In paced hearts, such stimuli evoked rises in left ventricular systolic pressure which were 2.3 times greater when applied to the left than to the right stellate ganglion. Tonic cardiac sympathetic impulses appear to funnel through the stellate ganglia. Decentralization of the stellate ganglia abolished the ventricular responses to stimulation of the carotid baroreceptors and cephalic ischemia. Approximately two thirds of the tonic and baroreceptor reflex influences to the left ventricle entered the stellate ganglia from lower segments of the thoracic paravertebral chain, and one third entered from the communicating rami of the stellate ganglia. The ratio of the effects of complete decentralization of the left to those of decentralization of the right stellate ganglion was 1.6, both with respect to eliminating sympathetic tone and abolishing the baroreceptor reflex.
Effect of Angiotensin on the Pressor Response to Tyramine in Normotensive Subjects and Hypertensive Patients
Authors: KANEKO YOSHIHIRO , TAKEDA TADANAO , NAKAJIMA KOUJI , UEDA HIDEO
Published: June 2012

Arterial blood pressure was recorded directly in 11 normotensive subjects, in 11 patients with essential hypertension and in 10 patients with renovascular hypertension. The pressor response to intravenous injections of norepinephrine, tyramine, angiotensin and ephedrine was compared in these three groups. An infusion of angiotensin was then given and the pressor response to injections of norepinephrine, tyramine, and ephedrine was again measured; in some cases, a comparison of the effects of the cold pressor test was made.

In normotensive subjects, angiotensin infusion caused a significant increase in the responses to tyramine and ephedrine but not to norepinephrine; this occurred with subpressor doses and was unrelated to the level of blood pressure. In patients with renovascular hypertension, the mean pressor responses to injections of tyramine and ephedrine and the ratio of response to tyramine to that to norepinephrine were significantly increased, and the infusion of angiotensin failed to cause any further increase in these responses. In contrast, in patients with essential hypertension, the average response to injections of tyramine was not significantly increased, but during angiotensin infusion the response to tyramine increased as in normotensive subjects. It is proposed that increased response to tyramine, and lack of the potentiating effect of angiotensin demonstrated in renovascular hypertension, may be caused by increased formation of endogenous angiotensin due to renin secretion in this disease.
Cardiac and Respiratory Effects of Aortic Arch Baroreceptor Stimulation
Authors: LEVY MATTHEW N. , NG MANUEL L. , ZIESKE HARRISON
Published: June 2012

The reflex cardiac and respiratory effects of stepwise pressure variations in the isolated aortic arch were determined in anesthetized dogs. Elevation of pressure in the aortic arch depressed respiratory movements, decreased heart rate in the unpaced heart, and diminished peak pressure in the paced, isovolumetric left ventricle preparation. The threshold for these reflex effects was an aortic arch pressure of approximately 100 mm Hg. The maximum rate of change of these variables as a function of aortic arch pressure occurred at a pressure of about 175 mm Hg. Aortic arch pressures of 300 mm Hg or more were necessary to achieve maximal reflex effects. Heart rate changes were mediated by parasympathetic pathways predominantly, although reciprocal sympathetic influences were also involved. Both divisions of the autonomic nervous system mediated the effects upon ventricular performance.
Autonomic Influences on Cardiac Function in the Newborn Lamb
Authors: DOWNING S. EVANS , GARDNER THOMAS H. , SOLIS ROBERT T.
Published: June 2012

The influences of reflexly induced changes of sympathetic outflow to the heart on left ventricle contractility, heart rate, and systemic vascular resistance were studied in 26 technically successful experiments with newborn lambs ranging in age from 1 to 11 days. Reduction of brachiocephalic artery perfusion pressure was associated with a large increase of heart rate and of systemic vascular resistance. Under conditions of constant aortic pressure, heart rate and cardiac output, cephalic hypotension in most preparations induced a rapid onset of a fall of left ventricular end-diastolic pressure and an increase in the maximal rate of rise of left ventricular pressure (dp/dt max). Ventricular function curves obtained under conditions of constant aortic pressure and heart rate were shifted to the left. The average increase of stroke volume at left ventricular end-diastolic pressure of 10 cm H
2
O (SV
10
) was 23.3%, and of dp/dt max was 30.7% in the reactive preparations. The average of the largest responses for each preparation was an increase of SV
10
of 42%, and for left ventricular dp/dt max, 48.8%. Three preparations previously subjected to carotid sinus nerve sectioning showed similar responses. No evidence for diminution of the response following parasympathetic blockade with atropine was found. In all preparations, ganglionic blockade virtually or completely eliminated the response.
Alterations in Resting Length-Tension Relations of Cardiac Muscle Induced by Changes In Contractile Force
Authors: SONNENBLICK EDMUND H. , ROSS JOHN , COVELL JAMES W. , BRAUNWALD EUGENE
Published: June 2012

Effects of sustained postextrasystolic potentiation (P.S.), norepinephrine (NE), and calcium on resting length-tension relations of heart muscle were studied in the cat papillary muscle and isovolumic dog ventricle. In papillary muscles, P.S., calcium or NE produced no change in diastolic compliance when the muscles were freely isotonic, or afterloaded, and force remained constant. However, under isometric conditions, P.S. induced a small fall in diastolic tension while systolic force rose. Similar decrements in diastolic tension were observed when force of contraction was augmented by simply increasing afterload from a constant initial muscle length.

In the isovolumic ventricle, P.S., NE, and calcium each induced substantial increments in developed pressure, accompanied by small decreases in end-diastolic pressure. The latter was reduced or abolished by augmenting the initial contractile state with calcium or NE, so that the super-imposition of P.S. induced only trivial increments in developed pressure.

It is concluded that P.S., calcium, or NE do not induce changes in the resting length-tension relations of heart muscle per se. However, resting length at any given resting tension does increase slightly upon the augmentation of systolic force alone. It is postulated that these findings may be explained by the existence of a series viscous component.
Movement of Labeled Cholesterol Between Plasma Lipoprotein and Normal Arterial Wall across the Intimal Surface
Authors: DAYTON SEYMOUR , HASHIMOTO SAM
Published: June 2012

Normal rat aortas were incubated with their intimal surfaces in contact with a lipoprotein solution containing isotopically labeled free cholesterol. Uptake of cholesterol by the tissue increased with increasing concentration toward a plateau level. Maximum uptake of free cholesterol was estimated to be 13 µg/cm
2
per 24 hours, and uptake at physiological cholesterol concentration was 7.9 µg/cm
2
per 24 hours. Aortas containing labeled cholesterol were prepared by intragastric administration of cholesterol-7α-
3
H to normal rats. Experiments in vitro with these aortas demonstrated that efflux across the intimal surface was dependent upon presence of lipoprotein in the medium. This efflux was not retarded by prior boiling of the tissue. These results support suggestions that movement of labeled free cholesterol from plasma into the arterial wall may be largely the result of a physicochemical exchange between lipoprotein and endothelium.
Ventricular Volume of Nonbeating Excised Dog Hearts in the State of Elastic Equilibrium
Authors: BRECHER G. A. , KOLDER H. , HORRES A. D.
Published: June 2012

The volume in the left ventricle and that in the right ventricle were measured statically starting from zero transmural pressure, when the ventricle is in the state of elastic equilibrium, to a negative transmural pressure of 30 mm Hg. Freshly excised dog hearts were submerged in Ringer's solution at 10°C to establish zero transmural pressure, to offset the contribution of the weight of the ventricular walls on the shape of the ventricle, and to retard the onset of postmortem changes. The volume was approximated by an equation which included a power function of the body weight and another of the ventricular weight. For male dogs, the left ventricle when in the state of elastic equilibrium contained a mean volume of 14.5 ml for a body weight of 10 kg and a ventricular weight of 58 g; the corresponding figure for the right ventricle was 12.2 ml. In a quiescent heart below a certain ventricular volume, potential energy will be stored in structural elements of the ventricle wall that will facilitate the filling of the ventricle.
Mechanical Increase of Vascular Resistance in Experimental Myocardial Infarction with Shock
Authors: KUHN LESLIE A. , KLINE HOWARD J. , MARANO ANTHONY J. , HAMBY ROBERT I. , CESTERO JORGE , COHN LAWRENCE J. , WEINRAUCH HARRY , BERGER MARVIN
Published: June 2012

The hemodynamic and cardiac metabolic effects of increasing central aortic pressure by obstructing the abdominal aorta with a balloon catheter introduced via a femoral artery were determined in 28 anesthetized dogs with acute myocardial infarction and shock produced by coronary embolization with plastic spheres. Following coronary embolization, aortic pressure, cardiac output, and left ventricular mechanical efficiency declined in all animals; left ventricular "excess lactate" appeared in about one-half. With abdominal aortic obstruction for 1 hour, there were significant elevations of postembolic aortic pressure, coronary flow, cardiac output, left ventricular oxygen consumption and mechanical efficiency. Left atrial pressure rose slightly but not beyond normal limits. Arterial-coronary sinus oxygen difference diminished, and left ventricular excess lactate diminished or disappeared in 60% of the animals in which it was noted in the postembolic state. After 1 hour of abdominal aortic obstruction, cardiac output, central aortic pressure, and coronary flow diminished moderately. It is concluded that mechanical increase of vascular resistance for periods up to 1 hour may improve myocardial performance in acute myocardial infarction with shock. The increased left ventricular oxygen needs are met adequately by the increase of coronary flow associated with the increase of perfusion pressure.
Disturbances of Rhythm in the Cold-Blooded Heart Under Aconitine
Authors: TENNEY S. M. , WEDD A. M.
Published: June 2012

The cold-blooded auricle under aconitine shows an early profound depression in rhythmicity but recovers in from 5 to 10 minutes to develop a high rate of spontaneous beating which may be considered a tachycardia for this preparation. Although arrhythmias do not appear spontaneously, a single, properly-timed stimulus to the auricle under aconitine initiates a multiple response which appears like ordinary fibrillation or flutter. The alterations in fundamental properties of the auricle which are required to elicit multiple responses favor a re-entrant rather than a focal mechanism of the induced arrhythmia.
Renal Inhibition of Pressor Responses to Drugs
Authors: MCCUBBIN J. W. , PAGE IRVINE H.
Published: June 2012

Bilateral nephrectomy selectively augments reactivity to pressor drugs and affects that to angiotonin the most prominently. This change is not mediated through the central nervous system, does not depend upon mechanical exclusion of the renal vascular bed, and is not modified by change in sodium intake. The inhibitory action on pressor responsiveness is independent of renal excretory function.
Effect of Cortisone and ACTH on Blood Pressure of Hypotensive, Potassium-Deficient Rats
Authors: FREED S. C. , ROSENMAN R. H. , GEORGE SHIRLEY ST. , SMITH MALCOLM K.
Published: June 2012

Potassium deficiency, induced in a series of rats by dietary deprivation, was associated with a depressor response. The administration of cortisone and, to a lesser extent, of corticotropin (ACTH), promptly elevated their lowered blood pressures. The possible participation of the adrenal cortex in the depressor response to potassium deficiency is discussed.
Sensitization of Individual Vascular Territories to the Antiphlogistic Effect of Hydrocortisone
Authors: SELYE HANS
Published: June 2012

Experimental interference with the circulation in a circumscribed tissue area, too slight to produce any manifest disturbance in itself, can strikingly alter topical reactivity to irritants and to the antiphlogistic effect of hydrocortisone. Thus, certain vascular territories can be "selectively conditioned" to the anti-inflammatory actions of blood-borne corticoids. Conversely, when tissue damage is severe, such "selective conditioning" may induce a seemingly paradoxic reversal of the hydrocortisone effect, so that the hormone enhances inflammation. Here, impairment of circulation and hydrocortisone facilitate the production by irritants of necrosis, more than of inflammation. The resulting wide-spread necrosis induces an even greater inflammatory response, despite hydrocortisone, than would have been observed without hormone treatment.
The Temporal Course of Fluid Intake and Response to Fluid Loads in Perinephritic Hypertension in Rats
Authors: GREEN D. M. , STURTEVANT F. M. , VAN ARMAN C. G.
Published: June 2012

The spontaneous intake of water and saline and their output under load were measured in the early and late stages of perinephritic hypertension in rats. The conclusion was drawn that sodium exchange is increased in the prehypertensive phase, but reverts toward or drops below normal with the development of chronic sustained hypertension.