bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Two Murine Models of Familial Hypertrophic Cardiomyopathy
Authors: McConnell Bradley K. , Fatkin Diane , Semsarian Christopher , Jones Karen A. , Georgakopoulos Dimitrios , Maguire Colin T. , Healey Michael J. , Mudd James O. , Moskowitz Ivan P. G. , Conner David A. , Giewat Michael , Wakimoto Hiroko , Berul Charles I. , Schoen Frederick J. , Kass David A. , Seidman Christine E. , Seidman J. G.
Published: June 2012

Abstract
—Although sarcomere protein gene mutations cause familial hypertrophic cardiomyopathy (FHC), individuals bearing a mutant cardiac
myosin binding protein C
(
MyBP-C
) gene usually have a better prognosis than individuals bearing β
-cardiac myosin heavy chain
(MHC) gene mutations. Heterozygous mice bearing a cardiac MHC missense mutation (αMHC
403/+
or a cardiac MyBP-C mutation (MyBP-C
t/+
) were constructed as murine FHC models using homologous recombination in embryonic stem cells. We have compared cardiac structure and function of these mouse strains by several methods to further define mechanisms that determine the severity of FHC. Both strains demonstrated progressive left ventricular (LV) hypertrophy; however, by age 30 weeks, αMHC
403/+
mice demonstrated considerably more LV hypertrophy than MyBP-C
t/+
mice. In older heterozygous mice, hypertrophy continued to be more severe in the αMHC
403/+
mice than in the MyBP-C
t/+
mice. Consistent with this finding, hearts from 50-week-old αMHC
403/+
mice demonstrated increased expression of molecular markers of cardiac hypertrophy, but MyBP-C
t/+
hearts did not demonstrate expression of these molecular markers until the mice were >125 weeks old. Electrophysiological evaluation indicated that MyBP-C
t/+
mice are not as likely to have inducible ventricular tachycardia as αMHC
403/+
mice. In addition, cardiac function of αMHC
403/+
mice is significantly impaired before the development of LV hypertrophy, whereas cardiac function of MyBP-C
t/+
mice is not impaired even after the development of cardiac hypertrophy. Because these murine FHC models mimic their human counterparts, we propose that similar murine models will be useful for predicting the clinical consequences of other FHC-causing mutations. These data suggest that both electrophysiological and cardiac function studies may enable more definitive risk stratification in FHC patients.
Adenoviral Expression of Vascular Endothelial Growth Factor-C Induces Lymphangiogenesis in the Skin
Authors: Enholm Berndt , Karpanen Terhi , Jeltsch Michael , Kubo Hajime , Stenback Frej , Prevo Remko , Jackson David G. , Yla-Herttuala Seppo , Alitalo Kari
Published: June 2012

Abstract
— The growth of blood and lymphatic vasculature is mediated in part by secreted polypeptides of the vascular endothelial growth factor (VEGF) family. The prototype VEGF binds VEGF receptor (VEGFR)-1 and VEGFR-2 and is angiogenic, whereas VEGF-C, which binds to VEGFR-2 and VEGFR-3, is either angiogenic or lymphangiogenic in different assays. We used an adenoviral gene transfer approach to compare the effects of these growth factors in adult mice. Recombinant adenoviruses encoding human VEGF-C or VEGF were injected subcutaneously into C57Bl6 mice or into the ears of nude mice. Immunohistochemical analysis showed that VEGF-C upregulated VEGFR-2 and VEGFR-3 expression and VEGF upregulated VEGFR-2 expression at 4 days after injection. After 2 weeks, histochemical and immunohistochemical analysis, including staining for the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), the vascular endothelial marker platelet–endothelial cell adhesion molecule-1 (PECAM-1), and the proliferating cell nuclear antigen (PCNA) revealed that VEGF-C induced mainly lymphangiogenesis in contrast to VEGF, which induced only angiogenesis. These results have significant implications in the planning of gene therapy using these growth factors.
Effect of Hypothermia on Experimentally Produced Arrhythmias
Authors: BEYDA EZRA J. , ALVAREZ SOL , MULLER OTTO F. , BELLET SAMUEL
Published: June 2012

The effect of hypothermia on experimentally produced rapid arrhythmias in the dog was studied. Rapid ectopic rhythms were produced in open-chest and "intact" animals by application of aconitine solution to the right atrial wall. In all experiments, a beneficial cardiac effect was obtained: marked slowing of the ventricular rate occurred in all cases, and in approximately half of the cases sinus rhythm was restored. On rewarming, although the heart rate increased, the sinus rhythm acquired during hypothermia persisted in most instances. The blood pressure fell when a rapid arrhythmia was produced. A further drop was observed in approximately half the cases during hypothermia. In the remaining cases no change, or a slight rise in blood pressure, occurred during cooling. The results obtained in the experimental animal would appear to have a bearing on the therapy of certain refractory arrhythmias in the human subject.
Effect of Hypothermia on the Tolerance of Dogs to Digitalis
Authors: BEYDA EZRA J. , JUNG MAREK , BELLET SAMUEL
Published: June 2012

The tolerance to digitalis was studied in eight dogs during hypothermia and compared to that of six normothermic animals. The average lethal dose of Digoxin for the dog under hypothermia was found to be approximately double that of the normothermic dog. Thus, hypothermia significantly increases the tolerance of the drug. The possible explanation for this finding is discussed. It appears that hypothermia, by its direct effect on myocardial metabolism, might counteract the toxic effects of digitalis. Potassium, affected by both hypothermia and digitalis, is also a possible factor. The clinical implications of this finding are discussed.
Effect of Bretylium Tosylate (Darenthin) on Pulmonary Circulation
Authors: HALMAGYI D. F. J. , COLEBATCH H. J. H.
Published: June 2012

In a dose sufficient to produce a mild systemic hypotension, bretylinm increases pulmonary arterial pressure and venous admixture in the experimental animal. The clinical significance of these side effects appears to deserve some consideration.
Experimental Assessment of Technique for Measurement of Valvular Regurgitation by Constant Infusion of Indicator
Authors: ARDITI LUCEIN I. , PEARCE CHARLES W. , WINSTON A. LEE , LUKAS DANIEL S.
Published: June 2012

The continuous infusion of indicator into the left ventricle at a constant rate, with comparison of indicator concentration in aortic and left atrial blood at equilibrium prior to recirculation, is theoretically a valid method for measurement of mitral regurgitation. When assessed in dogs with constantly metered left ventricular-atrial regurgitation, however, the method failed to measure regurgitation accurately and yielded values which, in general, were well below the true ones. The failure of the method appeared to be due to incomplete dispersion of dye in the ventricle and limited distribution of regurgitated blood within the atrium. Despite differences between the animal preparation and naturally occurring mitral regurgitation, the study casts doubt on the quantitative reliability of data on valvular regurgitation in man obtained by indicator methods utilizing left ventricular injection and left atrial sampling.
Effect of Age on the Changes of Extracranial Circulation During Hypoxia
Authors: SIMONSON ERNST
Published: June 2012

In 68 healthy older men (mean age 59.5 years), the peak amplitude of impedance plethysmographic pulse tracings from the forehead increased significantly during hypoxia (breathing a 10 per cent O
2
, 90 per cent nitrogen mixture), while there was no significant change in a group of 58 healthy young men (mean age 23.4 years). The height of the dicrotic notch increased in the older men and decreased in the younger men. In both groups, the cycle length decreased, and the relative peak time increased significantly during hypoxia. The absolute peak time decreased in the older group and did not change in the younger group. The amplitude changes in hypoxia were related to the decrease of arterial oxygen saturation in the older, but not in the younger, men. It is suggested that hypoxia is a stronger stimulus for the reaction of extracranial circulation in older subjects.
Effect of Various Adrenal Steroids on the Electrocardiogram of Adrenalectomized Dogs
Authors: DAVANZO JOHN P. , CROSSFIELD H. C. , SWINGLE W. W.
Published: June 2012

The effects of large amounts of various adrenal steroids on the electrocardiogram of the adrenalectomized dog are described. The changes which occurred most frequently fell into 2 major groups: (1) those following excess of mineralo-corticoids, e.g., desoxycorticosterone and aldosterone, and (2) those appearing after gluco-corticoid administration. A characteristic type of diphasic T wave frequently followed treatment with hydrocortisone and its analogs, and its correction was hastened by substituting mineralo-corticoid therapy.

The 3 analogs of hydrocortisone (dexamethasone, prednisolone and triam$$$inolone) induce similar electrocardiographic patterns and after prolonged administration alter the P-Q interval in varying degrees, but more frequently produce a diphasic T. Dexamethasone preserves the normal pattern longer than the other steroids tested.
Evaluation of Blood Volume Measurement Techniques
Authors: REMINGTON JOHN W. , BAKER CARLETON H.
Published: June 2012

To assess the ability of an injection of Cr
51
-tagged red cells and one of T 1824 to measure a standard part of the total blood volume, two types of experiments have been done. First, three or four successive injections were made, separated by the sampling period of 80 minutes, in both intact and splenectomized dogs under different anesthetic regimes. The tagged cells gave total cell volumes showing no trend away from the expected value, based on the first determination and the cells lost in the sample taken, and the standard deviation was but 3.0 per cent. There was no real difference in this error depending upon the anesthesia. The T 1824 measured plasma volume tended to become progressively greater than the expected value with each injection. This trend could not be corrected out on the basis of either a plasma specific gravity or a hematocrit change. The standard deviation was three times larger than for the cell volume. Part of this variability might be related to fluctuations in dye concentration away from the bestfit slope, as were quite common at various times during the sampling period. Yet, plasma volumes based on the concentration shown at any particular time (e.g., 10 minutes) gave slightly worse agreement with the expected. The second experiment involved measurements of cell and plasma volume after three successive bleedings. Here both volumes were greater than the expected, with the standard deviation of the cell volume still less than that of the plasma volume. Curiously enough, T 1824 could follow the changes in plasma volume in these bleeding experiments a little better than it could reproduce the same volume in essentially normovolemic dogs.
Influence of Carotid Baroreceptors and Vasoactive Drugs on Systemic Vascular Volume and Venous Distensibility
Authors: ROSS JOHN , FRAHM CHARLES J. , BRAUNWALD EUGENE
Published: June 2012

Changes in systemic vascular volume, in venous return, and in the distensibility of the venous system were studied in an experimental canine preparation. The use of an extracorporeal circulation permitted complete exclusion of the heart and lungs and allowed continuous measurement of alterations of intravascular blood volume and of venous return to the oxygenator. Brief occlusion of the venous outflow line permitted the inscription of venous pressure-volume curves. Hypotension in the isolated carotid sinuses, the administration of catecholamines or of acetylcholine resulted in venoconstriction, evidenced by a decrease in vascular volume, an increase in venous return, and flattening of the venous occlusiou curves. Conversely, carotid sinus hypertension or the administration of trimethaphan produced venodilatation, a decline in venous return, and an increase in vascular volume. The significance of these observations in the regulation of cardiac output is discussed.
Effect of Guanethidine and Bretylium on the Dog Heart-Lung Preparation
Authors: GAFFNEY TOM E.
Published: June 2012

Inotropic and chronotropic effects of guanethidine and bretylium have been observed in heart-lung preparations made from normal and chronically reserpinized dogs. Guanethidine (0.3 to 30 mg.) in the untreated preparation had marked positive inotropic and chronotropic effects, whereas after pretreatment with reserpine it had a striking negative inotropic effect and no effect on heart rate. Guanethidine given to preparations made from animals pretreated with guanethidine had a negative inotropic effect smaller than that seen after reserpine pretreatment. Bretylium (0.3 to 30 mg.) in the untreated preparation had both positive inotropic and positive chronotropic effects. In the chronically reserpinized animal, the positive inotropic effect of bretylium persisted though it was reduced to about one-quarter of the original size. The positive chronotropic effect of bretylium in this circumstance was reversed to a negative chronotropic effect. These effects are interpreted as indirect but strong evidence that: (1) guanethidine and bretylium exert at least part of their initial positive inotropic and chronotropic effects by a release of catecholamines; and (2) in the amine-depleted heart, guanethidine has an intrinsic negative inotropic effect, whereas bretylium has an intrinsic positive inotropic effect.
Regional Distribution of Myocardial Blood Flow in the Dog as Determined by Rb
86
Authors: LEVY MATTHEW N. , DE OLIVEIRA JORGE MARTINS
Published: June 2012

The distribution of Rb
86
Cl in the canine myocardium was determined at 20 seconds, 10 minutes, and 19 hours after administration of isotope. The uptake of Rb
86
20 seconds after injection is related to blood flow, and the myocardial distribution of isotope probably closely reflects the apportionment of coronary blood flow. The isotope was uniformly divided between the various regions of the left ventricle and averaged 6.4 per cent of the injected dose per 100 Gm. of tissue. This value exceeded the fractional uptake of 4.3 per cent for the right ventricle and 3.7 per cent for the atria.

After 19 hours, the Rb
86
content serves virtually as a tracer for potassium. After this interval, the myocardial distribution of Rb
86
closely followed previously published reports of the relative potassium contents of the various myocardial regions.
Interpretation of the Appearances of the Small Pulmonary Blood Vessels in Animals
Authors: BEST P. V. , HEATH D.
Published: June 2012

A study was made of the histology of the small pulmonary blood vessels in uninflated postmortem specimens from the monkey, dog, fox, mouse, rat, rabbit, squirrel, sheep, pig, cow, seal, kitten, eivet, and guinea pig. The small pulmonary arteries appeared unusually muscular compared to those of man, and the increased medial thickness was reminiscent of the medial hypertrophy found as an early change in the human lung in diseases asso ciated with pulmonary arterial hypertension.

This suggests to us that the histological cri teria usually employed for grade 1 hyperten sive pulmonary vascular disease in man are invalid when applied to lung biopsies from animals used for experiments on the pulmo nary circulation. There is a sphincter-like arrangement of the muscle of the media of the muscular pulmonary arteries of the guinea pig. In the rat, mouse, and squirrel there is an extension of cardiac muscle along the larger intrapulmonary veins. Fibromuscu Ear prominences project into the vein lumen iii the cow and the pig.
Indicator-Dilution Curves During Methoxamine Infusion jn Patients with Mitral Valvular Disease
Authors: YU PAUL N. , FINAYSON JAMES K. , LURIA MILTON N.
Published: June 2012

This report describes the time-concentration components and the contour of indicator-dilution curves recorded from the femoral artery after injection of radioactive iodinated (I
131
) human serum albumin into the pulmonary artery before and during methoxamine infusion in nine patients with predominant mitral stenosis, and seven patients with predominant mitral insufficiency.

During methoxamine infusion, the changes were as follows: (a) The forward cardiac output was uniformly reduced in both groups. The changes in the total and "central" blood volumes were inconsistent in both groups. In all cases, there was prolongation of the appearance and mean transit times. (b) There was a significantly greater prolongation of the reciprocal of the downslope and the disappearance time in patients with mitral insufficiency than in those with mitral stenosis. By means of a simple formula, we allowed for alteration in forward cardiac output and "central" blood volume during methoxamine infusion, and a satisfactory discrimination between mitral stenosis and mitral insufficiency was achieved by comparing the change in 1/S.

Comparison of the ratio of spread time to appearance time (T
s
/T
A
) before and during methoxamine infusion also effected an excellent separation between the two groups. It is postulated that the characteristic changes of the indicator-dilution curves during methoxamine infusion in patients with mitral insufficiency were due to augmentation of regurgitant stroke volume, increase in the force of the regurgitant jet, or both.
Site of Action of Hypertonic Saline in the Pulmonary Circulation
Authors: ELIAKIM M. , STERN S. , NATHAN H.
Published: June 2012

The effect of intravenous injections of 20 per cent saline on the pulmonary circulation was examined in 19 dogs. A marked rise of pulmonary arterial pressure was recorded in all cases. The pressure changes in the pulmonary veins depended largely on the choice of the vein for pressure measurements. A hypertensive response was usually recorded in the superior vein, while in the inferior vein no change or a slight fall in pressure was the rule. Left atrial pressure either did not change or fell.

A difference in the anatomical structure of the muscle sphincter around the superior and inferior pulmonary veins is described. A potent sphincter surrounds the superior veins and infiltrates within their walls some-times as far as the border of the lung. The sphincter around the inferior veins is rudimentary and inconspicuous.

Evidence is brought that hypertonic saline acts both on the pulmonary veins close to the left atrium and at the pulmonary arteriolar level.
Method for Study of Contraction of Isolated Heart Muscle Under Various Physical Conditions
Authors: BLINKS JOHN R.
Published: June 2012

Since the actions of physical and chemical influences upon myocardial contractility are not necessarily independent, study of interactions between the two may give clues to the mechanisms of action of both. A method is described for study of the interrelations of temperature, the interval between contractions, distending pressure, volume, amplitude of contraction against constant pressure, and pressure generated by contraction at constant volume in isolated thin-walled cardiac chambers. Unusual features are the use of gas as a distending medium and a volume recorder which measures the conductance of the fluid displaced by the chamber. As illustrations of use of the method, observations on some fundamental properties of rabbit atria are presented. Hysteresis and slow yielding to stress are prominent. The passive pressure-volume relationship is not affected by contractions against constant pressure, but is changed slightly by contractions at constant volume. The Starling curve of the isolated rabbit atrium always has a descending limb at high atrial volumes. However, the distending pressures required to produce a prominent descending limb are so high that their application causes irreversible changes in the muscle.
Kinetics of Blood Protein Leakage in Inflammation
Authors: ASCHHEIM EMIL , ZWEIFACH BENJAMIN W.
Published: June 2012

A method has been developed for following the course of the inflammatory reaction by assaying the radioactivity changes of the skin of rats injected intravenously with radioiodinated human serum albumin (RISA). For this purpose, the term "clearance" has been introduced. It defines the amount of blood, in milliliters, completely cleared of radioactive material by 1 Gm. of dry skin. The initial reaction follows strictly a course described by the formula a = b t
c
, where (a) is the difference between the average clearance of the inflamed and normal skin samples, (t) is the time in minutes, and (b) and (c) are constants. For normal-, medium-, and large-sized rats, as well as adrenalectomized animals, subjected to Xylene irritation, the (c) value was characteristically constant and equal to 2. Heat injury, on the other hand, is characterized by a lower exponent. The value of the constant (b) varied with the experimental group. The functional or anatomical factors reflected in these constants are not established.

Nutritional blood flow was determined at close intervals during the development of the inflammatory reaction. It is postulated that the characteristic kinetics of the transudation of blood proteins into the inflamed skin reflects the changes in nutritional blood flow and vascular-exchange area which accompany the development of the reaction. The view is expressed that the passage of smaller molecules across normal vessel walls is likewise regulated by changes in blood flow and extent of vascular exchange.
Coronary Arteriosclerosis Induced in Young Dogs by Prolonged Intra-aortic Infusions of Serotonin
Authors: ROSSI PAOLO , STEVENSON MAUDE , KHAKSAR PARVIZ , BELLET SAMUEL
Published: June 2012

The cardiac effects of serotonin were studied in 20 young mongrel dogs. Serotonin was slowly infused through a catheter inserted into the left carotid artery with the tip of the catheter located 1 or 2 cm. above the coronary orifices. The doses for different groups of dogs were 10, 5, 2, and 1 mg. in 500 cc. of normal saline, three to six times each week. The period of infusion lasted one to six weeks. A group of four dogs acted as controls. In dogs treated for more than two weeks with doses of 10 to 5 mg., and in those treated for more than four weeks with doses of 2 mg., the following pathological findings were observed: (a) fibrotic thickening of mitral, aortic, and tricuspid valves in this order of frequency; (b) myocardial hemorrhages partially organized ; (c) focal ischemic necrosis of myocardium with or without round cell infiltrations; (d) intimal thickening of small coronary arteries either in the form of cushions bulging into the lumen or extensive subendothelial thickening with asymmetrical reduction of the lumen. The intima of these arteries showed either an acellular homogeneous substance or a fibroblastic proliferation and fibroelastic hyperplasia. These findings were considered to be related to a direct action of serotonin which plays some role in the connective tissue function.
Carotid Pulses and Peripheral Plethysmograms at Rest
Authors: DONTAS A. S. , SIMONSON ERNST
Published: June 2012

In 75 healthy men and 47 men with previous coronary occlusion (mean age for both groups 60.0 years), the right carotid pulses and an impedance plethysmogram of the forehead were recorded. There were no significant differences between the major items of the carotid pulse in the two groups, but the absolute and relative peak times of the forehead plethysmograms of the coronary group were shorter than those of the normal group of the same age, and more similar to the pulse contours in healthy younger population.

The correlation between the carotid pulse and the forehead impedance plethysmograms was highly significant for most items in the healthy group, whereas in the coronary group only the ratio of initial anacrotic break height to maximal pulse height was significantly correlated in the two pulses.

The results suggest a compensatory reaction of peripheral circulation in patients with previous coronary occlusion, and the possible mechanism is discussed.
Observations on the Pathogenesis of Spontaneous Inherited Hypertension and Constricted Renal-Artery Hypertension in Rats
Authors: LAVERTY RICHARD , SMIRK F. HORACE
Published: June 2012

A preparation is described in which blood is taken alternately from a pair of donor rats and perfused at constant rate through the same vascularly isolated, denervated recipient rat hind limb. The preparation, though sensitive to the vasoconstrictor agent released in acute renal hypertension, fails to detect any vasoconstrictor substance either in the blood of rats bred to develop hyper-tension spontaneously or in the blood of rats with chronic renal hypertension.

To study nervous tone in limb blood vessels, an innervated rat hind limb was perfused through a femoral artery with blood taken from the opposite femoral artery. After administration of hexamethonium, weight-corrected hind-limb perfusion pressures of spontaneous hypertensive (B), chronic renal hypertensive (CR), and control (C) rats (all series included) fall to the same average level. Hence, the component of the hind-limb peripheral resistance which is not neurogenically maintained must be of the same order of magnitude in all three groups. In B, CR, and C rats, the perfusion pressure falls after hexamethonium ; all have the same relationship to the height of the blood pressure at the time the perfusion pressure is measured, high blood pressures being associated with high perfusion pressures and low blood pressures with low perfusion pressures. Therefore, since the differences between the hind-limb peripheral resistances of B, CR, and C rats, as measured by the perfusion pressure, are removed by administration of hexamethonium, it follows that they depend upon differences in the neurogenically maintained component of the peripheral resistance. After hexamethonium the blood pressures of B and C rats fall to the same average level.
Measurement of Coronary Blood Flow Using Radioactive Iodine Compared with Nitrous Oxide
Authors: FORTE IVAN E. , SCHMITTHENNER JERRY E. , NEAL HUNTER S.
Published: June 2012

The short time required for arterial blood to pass from the heart through the coronary sinus requires fast recording. Curves recorded simultaneously from the precordium and from either the proximal pulmonary artery or the coronary sinus afforded no means for approximating coronary blood flow. These results are interpreted as indicating that the radioisotope-dilution method for the determination of coronary blood flow is impracticable in the dog, with our present instrumentation. This is because of the inherent uncertainty and the numerous technical difficulties involved in putting a bolus into a coronary artery and recording from coronary-sinus blood, when using as standards of reference a nitrous-oxide flow and the Fick cardiac-output measurements.
A Mathematical Model of Dilution Curves for Flow Study
Authors: GOTT F. S. , MOIR T. W. , MACINTYRE W. J. , PRITCHARD W. H.
Published: June 2012

The graphical method of estimating cardiac output and central circulating blood volume is reviewed. An electronic-integration modification is described for fast, accurate cardiacoutput estimation. A mathematical representation of biphasic dilution curves is developed and, based on this analysis, formulas are proposed for determination of cardiac output and central circulating blood volume. Clinical application of this determination method is shown, and its advantages are discussed.
Blood Flow in the Renal Medulla
Authors: LILIENFIELD LAWRENCE S. , MAGANZINI HERMAN C. , BAUER MARK H.
Published: June 2012

The accumulation of intra-arterially injected I
131
albumin in the papilla of the kidney was measured in a series of 33 anesthetized dogs producing hypertonic urine. Although the data were widely scattered, an estimate of the average rate of this accumulation during the first half-minute following the start of the infusion was made. From the data, the plasma perfusion rate in the papilla under the experimental conditions was calculated and appears to average 25 ml./100 Gm./min.
Changes in Peripheral Blood Flow Distribution in Healthy Dogs
Authors: RUSHMER ROBERT F. , FRANKIN DEAN L. , VAN CITTERS ROBERT L. , SMITH ORVILLE A.
Published: June 2012

The instantaneous velocity and the integrated flow through a splanchnic artery (superior mesenteric or hepatogastric), the renal artery, and the terminal abdominal aorta were recorded continuously and simultaneously, as were the mean aortic pressure and heart rate, during a wide variety of spontaneous cardiovascular adjustments of healthy active dogs. These responses were compared with the effects of infusing vasoactive substances, such as isoproterenol,
l
-epinephrine, norepinephrine, acetyichol lie, and Pitressiii, and with P to stimulation of selected sites in the base of the brain. During sponta neous activity, the flow through the splanch nic and renal arteries usually varied in a direction opposite to that of changes in flow to the hindciuarters. The changes in mesen teric or renal flow were relatively slight, even during strenuous exercise that produced a substantial increase in flow to the hindciuar ters. Vasoactive substances tended to produce changes in the same direction in all three beds. Changes in flow distribution and in wave forms of the instantaneous flow patterns produced by vasoactive substances did not resemble those produced by spontaneous ad justment. 1-lowever, stimulation of selected diencephalic sites (e.g., 112 fields of Forel) produced changes in both flow distribution and flow velocity patteras that closely simu lated those observed during exercise in the same animals. Stimulation in the same re gions was previously reported to produce changes in left ventricular performance also closely resembling those noted during tread mill exercise.
Angiotensin, the Renal Pressor Hormone
Authors: BUMPUS F. MERLIN , SMEBY ROBERT R. , PAGE IRVINE H.
Published: June 2012

We have shown the side groups of angiotensin that are necessary for biological activity. Additional evidence is given that angiotensin decapeptide has little or no biological activity and exerts its effect only through the octapeptide. Even though none of the analogues of angiotensin have inhibitory action on the parent compound, the information obtained from studying these compounds could lead to the synthesis of inhibitors.
Peripheral Venous and Arteriolar Responses to Infusions of Angiotensin in Normal and Hypertensive Subjects
Authors: WOOD J. EDWIN
Published: June 2012

The distensibility of the peripheral veins of the hypertensive subject is normal, that is, there is no evidence of peripheral venoconstriction, despite the excessive arteriolar constriction. The forearm veins of hypertensive patients respond to pooling of blood in the upright position to a lesser degree than do veins of normotensive individuals, indicating a lesser degree of smypathetic nervous activity in response to this stimulus. The peripheral veins of hypertensive subjects constrict normally in response to an infusion of norepinephrine, indicating that failure of venoconstriction in any circumstance cannot be attributed to failure of the smooth muscle of the veins.

Infusions of angiotensin produce constriction of the veins as well as the arterioles in normotensive individuals thus failing to mimic the naturally occurring state of essential hypertension. Infusions of angiotensin in hypertensive patients result in further arteriolar constriction and hypertension without concomitant venoconstriction. The results of these experiments suggest that peripheral venous responses of hypertensive subjects to angiotensin infusions may have been modified by previous exposure of these vessels to a material at least similar to angiotensin.
Sterol Metabolism in Monkeys
Authors: MANN GEORGE V.
Published: June 2012

The sensitivity of three primate species to a decompensation of sterol metabolism reflected by hypereholestereniia is demonstrated. The role of the dietary protein in this phenomenon is shown and explained as reflecting the supply of the precursors of cysteine, which in turn is essential to sterol metabolism.
Effects of Pneumonectomy on Pulmonary Circulation in Adult and Young Animals
Authors: RUDOLPH ABRAHAM M. , NEUHAUSER EDWARD B. D. , GOLINKO RICHARD J. , AULD PETER A. M.
Published: June 2012

Serial observations were made on the changes in pulmonary-artery pressure, radiological, and histological features of the pulmonary vasculature after pneiunonectomy or ligation of a single pulmonary artery in adult dogs and in puppies. Acute occlusion produced only insignificant changes in the pulmonary-arterial pressure. After one to two days, a rapid rise in pulmonary-arterial pres sure was observed. The pressure then gradually rose and in the subsequent months reached somewhat higher levels in the puppies as compared with the adult dogs. A decrease in pulmonary-arterial pressure which occurred after the initial rise in pressure was noted in one adult dog and two puppies. Comparison of the histology of the remaining lung with the control lung showed the development of medial hypertrophy of the smaller and medium-sized vessels, with an increase in the wall to lumen ratio. No significant difference was noted between the histological features of the adult and young animals. Pulmonary arteriograrns revealed progressive dilatation and tortuosity of the main pulmonary artery and its major branches, less striking in the puppies as compared with the adult dogs.
Some Circulatory Effects of Thoracotomy and Intermittent Positive Pressure Respiration in Dogs
Authors: FINLAYSON JAMES K. , LURIA MILTON N. , YU PAUL N.
Published: June 2012

In the anesthetized dog, thoracotomy and intermittent positive-atmospheric pressure (I.P.-A.P.) respiration produce a marked arid sustained fall in cardiac output. Evidence suggests that most of the fall is due to thora cotomy, and the I.P.-A.P. respiration at levels sufficient to maintain adequate ventilation plays a relatively minor part. Thoracotorny also results in considerable reduction of all compartments of the central blood volume, presumably due to loss of the distending ef fect of negative intrapleural pressure on the heart aiid great vessels. There was a consistent rise in pulmonary vascular resistance which was not significantly affected by the adminis tration of hexamethonium or phentolamine. It is suggested that humoral or neurogenic factors play a minor role in producing the in creased resistance.
Susceptibility of Rats with Renal Hypertension to Pyelonephritis, and Predisposition of Rats with Chronic Pyelonephritis to Hormonal Hypertension
Authors: HAJDU STEPHEN , LEONARD EDWARD
Published: June 2012

The principles and procedural details for assay of the biological activity of cardioglob ulin A, B and C are presented. In the Methods section are described the construction of the frog heart cannula, and the technique for can nulating the heart and cauterizing the atria. The principle and methods for assaying car dioglobulin B are described. The use of rat plasma as a source of eardioglobulin A and C in the assay is discussed. The basis for the cardioglohulin C assay is described. The prep aration of cardioglobulin B for use in the assay is described in detail. The procedure used in the cardiogl.obulin C assay is given, with a discussion of certain factors which must be controlled. The assay for cardio globulin A is outlined, and the method for preparing cardioglobulin C for use in the assay is also given. A comparison between cardioglobulin A and C activity in human subjects is made.
Interactions Among Dietary Fat, Protein, and Cholesterol in Atherosclerosis-Susceptible Pigeons
Authors: LOFDAND HUGH B. , CLARKSON THOMAS B. , GOODMAN HAROLD O.
Published: June 2012

In a 3x 2x 2 factorially designed experiment, White Carneau pigeons were kept nine months on diets containing three levels of protein (5 per cent, 15 per cent, and 30 per cent casein) and two types of dietary fat (10 per cent oil or 10 per cent hydrogenated coconut oil). Identical groups received, in addition, 0.25 per cent cholesterol. Analysis for serum cholesterol, and for cholesterol, total lipids, and phospholipids in the aorta, and measurements of atherosclerotic index were carried out. The data were subjected to statistical evaluation by analysis of variance. The addition of cholesterol to the diets elevated the level of cholesterol in the serum and the aorta and increased the severity of atherosclerosis. A significant interaction was found to exist between the type of fat in the diet and the presence or absence of cholesterol. Among cholesterol-fed birds only, corn oil exerted a significant cholesterol-lowering action. Suggestive evidence was obtained for the concept that the severity of atherosclerosis is influenced by the type of dietary fat, the level of protein, and the presence or absence of cholesterol in the diet, and that bio-logical interactions exist among these dietary variables.
Determination of the Pulmonary Capillary Blood Flow in Man
Authors: RIGATTO MARIO , RIGATTO GERARD M. , FISHMAN ALFRED P.
Published: June 2012

A method is described for the measurement of the pulmonary capillary blood flow in human subjects with normal lungs. The method depends on the performance of a vital capacity maneuver using nitrous oxide as the test gas. It attempts to circumvent the deficiencies of previous respiratory methods by using an infrared analyzer for the continuous measurement of the concentration of N
2
O in expired air, by ensuring that the respiratory maneuver is completed before recirculation occurs, and by determining simultaneously the values involved in the formula used for the calculation of the flow. As a basis for the method, the pulmonary recirculation time and the rate of N
2
O absorption by the lungs were measured separately. The values for the pul monary capillary blood flow obtained by the N
2
O method correlate well with those obtained by the direct Fick method: in 12 subjects, the average value by the N
2
O method was 5.65 L./min. in comparison with 5.55 L./min. by the direct Pick method; the mean Percentile deviation between the values obtained by the two methods in each subject was 11 per cent. The results obtained by the N
2
O method were also shown to be reproducible : In 14 subjects, successive measurements on the same occasion showed a mean percentile deviation of 6 per cent.
A Method for Electrocardiogram Wave-Pattern Estimation
Authors: CADY LEE D. , WOODBURY MAX A. , TICK LEO J. , GERTLER MENARD M.
Published: June 2012

Canine antisera to rabbit and hog renin were coupled to several fluorescein dyes. The antiserum was immunologically adsorbed once each with rabbit-liver and with bone-marrow powder, thereby removing excess dye and eliminating nonspecific staining. Mounted frozen-dried sections of kidneys from sodium- deficient rabbits (in which hyperplasia and hypergranulation of juxtaglomerular [JG] cells were present), from control rabbits, from a sodium-deficient dog, and from sodium-deficient rats were treated with the adsorbed labeled antiserum. Ultraviolet microscopy (direct technique) revealed an intense yel low-green fluorescence sharply limited to the granules of the juxtagloinerular cells in all sections studied from kidneys of rabbit and dog. JG granules in rats did not fluoresce, an observation in accord with the species spe cificity of renin.

The indirect ("sandwich") method was also employed (with adsorbed, labeled, rabbit antiserum to canine globulin), and although slight staining of gloinerular epithelium resulted, that in the JG granules was far more intense. In our hands, the faint glornerular staining was not blocked by prior treatment with unlabeled renin. Staining of JG granules in any kidney paralleled the intensity of JG granulation by light microscopy and the amount of extractable renin in the same kidney. JG-granule staining (direct and indirect techniques) was blocked by neutralization of the antirenin with renin. Heterogenous anti sera (to insulin; to human gamma globulin) failed to stain. Other rabbit tissues (heart, lung, liver) similarly treated with labeled antirenin never stained.

If this work can be repeated with immunologically pure renin, the evidence presented here, together with previously published studies from this and other laboratories, will establish beyond any reasonable doubt that the source of renin in the kidney is the juxtaglomerular cell, as postulated first by Goormagh tigh nearly a quarter of a century ago.
Sodium and Potassium Shifts Associated with Peripheral Resistance Changes in the Dog
Authors: JAMIESON JAMES D. , FRIEDMAN Sydney M.
Published: June 2012

The relation of changes in peripheral vascular resistance to blood sodium and potassium activity was studied in the dog hind limb. Arterial inflow was controlled by a constant output pump in the femoral artery line. Cations were monitored with glass-to-silver cannula electrodes in the venous outflow. Vasoactive drugs were administered intra-arterially in amounts sufficient only to affect the limb vasculature. Vasoconstrietion induced by norepinephrine or epinephrine was associated with a fall in blood (Na
+
) and often with a rise of (K
+
). Larger doses tended to produce a biphasic response in (Na
+
), a transient initial rise preceding the fall. Vasoconstrietion induced by serotonin or angio-tensin was associated with a fall in blood (Na
+
) unaccompanied by any consistent change in (K
+
). Vasoconstrietion induced by small amounts of pitressin (small series) produced a larger fall in (Na
+
) and rise in (K
+
) than with other agents producing an equal degree of vasoconstrietion. Vasodilatation induced by isoproterenol, acetylcholine, or histamine was accompanied by a rise in blood (Na
+
) without any consistent change in (K
+
).
Role of Intrarenal Venous Pressure in the Regulation of Renal Vascular Resistance
Authors: HINSHAW LERNER B. , WORTHEN DAVID M.
Published: June 2012

A series of eighteen experiments have been carried out on the heart-lung perfused dog kidney, and the results have defined the role of the intrarenal veins in the autoregulation phenomenon. It was found that there are a variety of intrarenal venous pressures which differ greatly according to (a) anatomical location and (b) the prevailing renal-artery pressure.

Findings have pointed out the importance of correct techniques in establishing the changes occurring in the intrarenal venous segment in response to an increase in renal artery pressure.

An increase in ureteral pressure results in a significant decrease in renal blood flow and an increase in overall renal vascular resistance, which further supports the role of extra-vascular pressure increases in renal-flow regulation.

The findings of the present study corroborate previous reports from this laboratory indicating that autoregulation is primarily accounted for on the basis of changes in renal extravascular pressure. Evidence has been provided for the absence of the "myogenie reflex" as a causal factor in autoregulation.
Importance of Transmural Pressure and Lung Volume in Evaluating Drug Effect on Pulmonary Vascular Tone
Authors: PATEL DALI J. , MALLOS ALEXANDER J. , DE FREITAS FLAVIO M.
Published: June 2012

The effect of norepinephrine (NE) on pulmonary vascular resistance (PVR) was studied in 11 thoracotomized dogs. Comparisons between the test and control states were made at corresponding average intravascular pressures in the pulmonary vascular bed and at the same airway pressure. A significant increase in PVR (
P
> 0.01) suggesting active vasoconstriction was found during NE administration.
Tolerance of Human and Rat Atrial Muscle to Hypothermia and Anoxia
Authors: NOREN GEORGE , GOLDRING DAVID , SLEATOR WILLIAM
Published: June 2012

Evidence is presented which strongly suggests the preservation of contractility of human atrial muscle when hypothermia of 25 to 31 C. is used during anoxia. Parallel studies were carried out on albino rat atria which gave results similar to that of the human tissue. This report adds further evidence that hypothermia is valuable in open-heart surgery when anoxic is indicated for the repair of cardiac malformations.
Relationships Among Intravascular Volume, Total Body Sodium, Arterial Pressure, and Vasomotor Tone
Authors: TAKAGI HIDEO , DUSTAN HARRIET P. , PAGE IRVINE H.
Published: June 2012

In rats made hyponatremic, hypovolemic, and hypotensive by intraperitoneal injections of 5 per cent glucose solution, arterial pressure was returned to control values by correction of the intravascular-volume deficit with either 5 per cent salt-free albumin or small volumes of hypertonic sodium-chloride solution. In the former, severe hyponatremia persisted; in the latter, it was corrected. Isotonic sodium-chloride solution, given in amounts considered sufficient to repair the extracellular-fluid and electrolyte deficits, was not so effective either in controlling hypotension or in expanding the intravascular volume. Using the height of the norepinephrine pressor response and the duration of the serotonin depressor phase as estimates of sympathetic activity, sympathetic vasomotor tone was found to be enhanced during hyponatremic, hypovolemic hypotension and depressed by administration of 5 per cent albumin, hypertonic and isotonic sodium-chloride solutions. These changes in estimates of sympathetic activity seemed dependent on changes in intravascular volume and not in extracellular sodium concentrations. Experiments performed following pentolinium-induced ganglion blockade showed that the depressor phase of the serotonin response was dependent on sympathetic vasomotor outflow, but that the height of norepinephrine pressor response was dependent not only on sympathetic activity, but also on the intravascular volume. In this study of selective sodium deficit, intravascular volume was found to be an important determinant of arterial pressure and sympathetic vasomotor tone.
Ability of Vasoconstrictor Drugs to Cause Adrenal Medullary Discharge after "Sensitization" by Ganglion Stimulating Agents
Authors: KANEKO YOSHIHIRO , MCCUBBIN JAMES W. , PAGE IRVINE H.
Published: June 2012

Administration of 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) subcutaneously, intravenously or into a lurnboadrenal artery for 20, or more, minutes in dosages that caused little, or no, change in arterial pressure caused the adrenal glands to respond to intravenous or local intra-arterial injection of vasoconstrictor drugs (angiotensin, norepi-nephrine, serotonin, vasopressin, phenyleph-rine, metaraminol, or barium chloride) by discharging large amounts of pressor material. Nicotine and tetramethylamnionium chloride given into a lumboadrenal artery had the same sensitizing effect; prolonged electrical stimulation of the cut peripheral end of the thoracic or lumbar sympathetic trunk or splanchnic nerve did not. Sensitization persisted during infusions or for at least one hour after subcutaneous administration of a ganglion stimulating agent. As after intravenous injection of a pressor drug, adrenal discharge caused reflex decrease of efferent sympathetic nerve activity. Following sensitization, partial constriction of a lumboadrenal artery proximal to the adrenal, or injection of potassium cyanide into the artery, produced responses comparable to those elicited by injection of vasoconstrictor drugs; carotid occlusion or electrical stimulation of the cut peripheral end of a splanchnic nerve did not cause the same large adrenal discharge. Partial constriction of the adrenal artery, or drug injection, did not cause adrenal discharge prior to administration of a ganglion stimulating agent. Discharge due to intra-arterial injection of a vasoconstrictor drug was prevented by simultaneous infusion of a vasodilator drug, sodium nitroprusside, into the adrenal artery. The sensitizing effect of the ganglion stimulating drugs was not prevented by atro-pine, ergotamine, spinal cord section at C6, splanchnic nerve section, or establishment of tachyphylaxis to vasopressin. It was eliminated for prolonged periods by injection of very small dosage of tetraethylammonium chloride or phentolamine into the adrenal artery. It is concluded tentatively that ganglion stimulating agents cause sensitization of receptors in, or near, the adrenal glands which, through a local neural mechanism containing a cholinergic synapse and an adrenergic receptor, respond to hypoxia by causing discharge of catechol amines.