bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping of the mouse atrial natriuretic factor gene. Evidence for tight linkage to the Fv-1 locus.
Authors: Mullins J J , Zeng Q , Gross K W
Published: June 2012

The importance of atrial natriuretic factor (ANF) in the regulation of salt balance and blood pressure is now widely recognized, and it would be extremely informative for both physiologists and molecular biologists to have mutants available that exhibit abnormal expression of this peptide hormone. The most direct mutation would affect the structural gene itself by altering either its coding potential or its regulation. With this aim in mind, it is of considerable interest to accurately determine the chromosomal position of the ANF gene (Anf) in the mouse. This information would permit a comparison with known mutations and provide a means of screening for mutations at this locus. Using recombinant inbred mouse strains, we undertook the mapping of the mouse Anf gene and demonstrated linkage of the gene to the Friend virus susceptibility-1 (Fv-1) locus on chromosome 4. The mapping was performed using a restriction fragment length polymorphism extant between the two parental strains. No recombination event between Anf and the Fv-1 locus was evident in any of the 34 strains tested. The assignment of Anf to this region of chromosome 4 coincides with the reported position of the cribriform degeneration mutation, which includes in its phenotype an abnormal electrolyte distribution. We have, therefore, begun studying this mutation to determine whether a defect in ANF expression is the underlying cause of the phenotype. Thus far, we have found no major DNA rearrangement close to the Anf gene.
Differential pressor and renal vascular reactivity to angiotensin II in spontaneously hypertensive and Wistar-Kyoto rats.
Authors: Guidi E , Hollenberg N K
Published: June 2012

The suggestion has been made that the Okamoto strain of spontaneously hypertensive rats (SHR) shares some features with a subgroup of patients with essential hypertension, called nonmodulators. One feature of nonmodulators is a renal blood flow response to angiotensin II (ANG II) that is blunted on a high salt diet; the blunted renal vascular response is corrected by converting enzyme inhibition. Renal blood flow (electromagnetic flowmeter) and pressor responses to graded ANG II doses (5-300 ng) were assessed in 24 SHR and 24 Wistar-Kyoto rats (WKY) ingesting 1.6% Na. In comparison to WKY, blood pressure was higher in SHR (155 +/- 4 vs 106 +/- 2 mm Hg; p less than 0.001), renal blood flow was lower (6.9 +/- 0.5 vs 8.2 +/- 0.4 ml/min/g; p less than 0.05), and the pressor response to ANG II was enhanced, (p less than 0.0005) but the renal vascular response was blunted (p less than 0.005). Captopril (1-30 mg/kg) reduced blood pressure more in SHR than in WKY but increased renal blood flow similarly in both strains. The blunted renal vascular response to ANG II in SHR was reversed by captopril, but inhibition of converting enzyme in the kidney did not parallel systemic inhibition. Maximum blockade of converting enzyme in the kidney appears to require a larger captopril dose than is required for systemic inhibition. These results suggest that the renal blood supply in SHR also shares some of the characteristics of nonmodulators and that the action of captopril on the renal blood flow probably reflects reversal of inappropriate intrarenal ANG II formation.
Analysis of the Radiocardiogram in Heart Failure
Authors: SHIPLEY REGINALD A. , CLARK RICHARD E. , LIEBOWITZ DANIEL , KROHMER JACK S.
Published: June 2012

A scintillation counter permits the use of very low doses of I
131
-albumin in the recording of radiocardiograms. In the presence of mild heart failure there is a distinct widening of the interval between the humps derived from the right and left heart. Application of the principle of three-compartment serial dilution suggests that this prolongation may be due in large part to reduced cardiac output; however, cardiac dilatation may contribute significantly. Although radiocardiographic tracings represent time concentration curves, wide angle counting over the heart does not permit a reliable direct estimate of cardiac output. The chief source of error lies in the variable contribution of surrounding extracardiac tissue to the total activity which is recorded.
Special Article: Factors Modifying the Contours of Indicator-Dilution Curves
Authors: Marshall Robert J.
Published: June 2012

Some of the factors that influence the contours and time components of indicator-dilution curves have been examined in dogs and man. These include the dynamic-response characteristics of the sampling-detecting-recording system, variations in the sampling site, quantity of blood and rate of blood flow between injection and sampling sites, vascular obstruction, and local and general alterations in peripheral blood flow. Any or all of these factors may be of importance in the interpretation of changes in indicator-dilution curves in patients with congenital or acquired heart disease.
Decrease of Venous Return Caused by Right Atrial Pulsation
Authors: Guyton Arthur C. , Langston Jimmy B. , Carrier Oliver
Published: June 2012

Over 250 records were made in 15 dogs to show the effect of artificially induced right atrial pressure pulsations on venous return. In not a single instance did the induced pulsations increase venous return, but often it decreased venous return. On the other hand, a very slight decrease in mean right atrial pressure down to the pressure level that the veins collapse completely was shown to increase venous return markedly. These experiments indicate that the benefit to venous return which results from rhythmic cardiac or respiratory suction is caused by a decrease in mean right atrial pressure.
Effects of Dopamine in Man
Authors: Horwitz David , Fox Samuel M. , Goldberg Leon I.
Published: June 2012

Dopamine, the biochemical precursor of norepinephrine, was infused intravenously into 11 normal subjects and 2 patients. Results of hemodynamic studies in 6 normal subjects indicated that dopamine increased cardiac output and stroke volume in all subjects. Arterial pressure also increased in all subjects with a predominant systolic pressure increment. Calculated vascular resistance decreased in 5 subjects and did not change in the other subject. Changes in heart rate were of small magnitude and were inconstant in direction. Left atrial pressure did not change in 2 patients at a time when substantial increments in cardiac output were produced by dopamine. Comparison of the doses of dopamine and norepinephrine calculated to produce equivalent increments in systolic pressure indicated that dopamine was 1/25 to 1/56 as potent as norepinephrine in this respect. Infusions of dopamine produced relatively small but consistent increments in blood glucose levels. It is concluded that the pharmacological actions of dopamine in man are different from those of epinephrine and norepinephrine. Because of its distinctive properties, dopamine may be useful in the treatment of patients with inadequate cardiac output.
Increased Vascular Reactivity in Experimental Hypertension
Authors: GORDON DAVID B. , NOGUEIRA ALFREDO
Published: June 2012

The responsiveness to norepinephrine of aortic strips from hypertensive rats and from normotensive rats was compared. The strips were set up in a bath of Krebs-Ringer solution, and isometric tension development upon addition of norepinephrine was recorded. The hypertensive strips produced the greatest tension, indicating a greater reactivity to norepinephrine. It was found that the initial tension exerted upon the strip greatly influenced its response, there being an optimal initial tension at which the greatest active response was obtained. These results support the hypothesis that hypertension may be due to an excessive reactivity of vascular smooth muscle.
Effects of Experimental Congestive Heart Failure, Ouabain, and Asphyxia on the High-Energy Phosphate and Creatine Content of the Guinea Pig Heart
Authors: FEINSTEIN MAURICE B.
Published: June 2012

The left ventricles of guinea pigs have been assayed for adenosine triphosphate, adenosine diphosphate, adenylic acid, phosphorylcreatine, free creatine, and inorganic phosphate. These determinations have been made under various experimental conditions which affect the performance of the heart in vivo, such as experimental congestive heart failure, acute asphyxia, and the influence of the cardiac glycoside, ouabain. In 20 guinea pigs with experimental congestive heart failure, sacrificed 1 to 18 days after surgically producing a coarctation of the ascending aorta, a significant fall in PC (54 per cent), ATP (24 per cent), and total creatine (34 per cent) was observed. The extent of the loss of high-energy phosphate compounds and total creatine paralleled the severity of cardiac failure as determined by abnormal intraventricular pressure pulses, ventricular hypertrophy, and gross and microscopic pathology. In animals with experimental congestive heart failure, the cardiac glycoside ouabain produced significant slowing of the heart, a positive inotropic effect, and a lowering of abnormally high right ventricular systolic and left ventricular diastolic pressures. At the height of the response to ouabain, there was a further fall in PC to 25 per cent of normal without any change in ATP concentration. The positive inotropic action of ouabain is, therefore, not due to an ability of the drug to increase high-energy phosphate levels in failing heart muscle. Acute asphyxia produces a very rapid fall in the PC concentration (85 per cent lost in two minutes) and a much slower fall in ATP (33 per cent lost in eight minutes). Recovery of normal mechanical activity, after a period of asphyxia, by rebreathing occurs with little, if any, restoration of ATP and at a time when the PC concentration is only about 25 per cent of normal. These experiments indicate that steady-state levels of high-energy phosphate compounds are not as important in determining the mechanical capacity of the heart as are their rates of synthesis.
Indicator-Dilution Studies with "Diffusible" Indicators
Authors: Chinard Francis P. , Enns Theodore , Nolan Mary F.
Published: June 2012

Some of the applications and extensions of the indicator-dilution technics have been presented. The technics offer possibilities for the investigation of some of the parameters of the circulatory and respiratory systems. They also offer a means of studying some of the more rapid features of organ metabolism in vivo. Compared to the degree of sophistication achieved by the more conventional dye-dilution studies, these extensions with "diffusible" indicators are in an embryonic stage of development. It is believed that they have a future.
Left Ventricular Function in Mammals of Greatly Different Size
Authors: Holt J. P. , Rhode E. A. , Peoples S. A. , Kines Helga
Published: June 2012

Studies of left ventricular volume and pressure have been carried out in the control state in four classes of intact anesthetized mammals (horses, cattle, swine, and dogs), body weights of which varied 54-fold. On the basis of these studies of both large and small hearts, extending over a wide range, a pattern of function for the left ventricle of all mammals has been described. Mathematical equations are given describing the interrelationships between left ventricular end-diastolic volume and end-systolic volume, stroke volume, cardiac output, stroke-work, heart rate, and total peripheral resistance.
Some Aspects of Occlusive Renal Arterial Disease in Man
Authors: Dustan Harriet P.
Published: June 2012

A review of the past six years' experience with the surgical treatment of hypertension associated with occlusive renal arterial disease has shown that in about 60 per cent of patients diastolic hypertension remitted, and in about 16 per cent arterial pressure was greatly reduced. In a small group of patients not operated upon, antihypertensive drugs were found to be as effective as in patients with essential hypertension; this suggests a neurogenic component in this type of renal hypertension.

Revascularization procedures in patients with unilateral renal arterial stenosis usually lessened disparities in glomerular filtration rate of the two kidneys but did not eliminate them. Postoperatively, solute and water excretions of the repaired kidney usually exceeded those of the unaffected side even though preoperatively they had been much less.

In a few patients, information concerning the natural history of renal arterial diseases shows that atherosclerosis need not necessarily cause progressive stenosis over periods as long as one year, and that the nonatherosclerotic lesions, segmental mural fibrosis and intimal sclerosis, once established, can exist without apparent change for as long as three years.
Effect of Chlorothiazide on Response of Renal Vascular Bed to Vasoactive Substances
Authors: Gillenwater Jay Y. , Scott Jerry B. , Frohlich Edward D.
Published: June 2012

In the anesthetized dog, administration of an isosmotic solution of chlorothiazide into the renal artery failed to affect renal vascular resistance but did acutely attenuate the constriction produced by intra-arterial injection of
l
-epinephrine, levarterenol, and Val-5-angiotensin II and potentiated the dilation produced by intra-arterial injection of MgCl
2
.
Content of Collagen, Elastin, and Water in Walls of the Internal Saphenous Vein in Man
Authors: Švejcar Jiří , Přerovský Ivo , Linhart Jiří , Kruml Jiří
Published: June 2012

Chemical analysis of the collagen, elastin, and water content of various segments of the internal saphenous vein in the human has been carried out. Normal values were obtained to give a basis for comparison with pathological material from varicosities. The following observations were made: (1) The ratio of connective tissue elements in the internal saphenous vein (ISV) is the reverse of that in the aortic wall; the ISV contains more collagen than elastin. (2) The total scatter of elastin and collagen values in the venous wall is large, mainly due to interindividual differences. No particular dependence on age was observed in the ambulant group. (3) Analysis of neighboring samples of vein in a given individual showed little variation. (4) There was a consistent difference in venous composition in a given individual between the superior segment at the insertion of the ISV into the femoral vein and the inferior segment at the level of the ankle. There was more collagen and elastin superiorly, and more muscle inferiorly. This corresponded to histological analysis showing a thicker layer of circular muscle in the media of the inferior segment. (5) The same differences in elastin content were found in infants who had not yet begun to walk; however, the infant group showed no superior-inferior differences in collagen and muscle composition of the venous wall. It is suggested that this latter difference is a function of upright posture and bipedal locomotion, and the attendant gradient of hydrostatic pressure.
Vasodilator Action of Guanethidine
Authors: Abboud Francois M. , Eckstein John W.
Published: June 2012

The cardiovascular effects of intravenous guanethidine were measured in animals treated with reserpine. The action of intraarterial guanethidine was studied also in perfused forelegs of dogs. The following conclusions were reached:

1. There was no significant increase in cardiac output, heart rate, or systemic arterial pressure following intravenous guanethidine in treated animals; only sustained vasodilatation was observed.

2. The vasodilatation was caused by a local action of the drug on vascular smooth muscle. The dilatation became more pronounced following depletion of catecholamines with reserpine and repeated administration of guanethidine.

3. The dilatation did not appear to be mediated through the release of catecholamines, histamine, or acetylcholine. It may have resulted, at least in part, from stimulation of
beta
adrenergic receptors or other "dilator receptors" which are blocked by dichloroisoproterenol.
Role of Pulmonary Lymphatics in Chronic Pulmonary Edema
Authors: Uhley Herman N. , Leeds Sanford E. , Sampson John J. , Friedman Meyer
Published: June 2012

Previously small increases in canine pulmonary lymph flow found in acute pulmonary venous hypertension were ineffective in preventing fatal pulmonary edema. Our objective was to determine if functional expansion of the pulmonary lymphatic system could occur over a period of time and possibly aid in preventing critical pulmonary edema. Chronic heart failure was successfully induced in ten dogs by creating an aorticocaval anastomosis and administrating desoxycorticosterone trimethylacetate and a salt-rich diet. Pulmonary lymph flow was obtained at the time of sacrifice by tapping an isolated lymph-collecting chamber produced in the right external jugular vein. Gross increases in pulmonary lymph flow, varying from 300 to 2,800 per cent over the normal flow of 4 ml./hr., were found in 7 of the 10 dogs. These observations indicate that important functional expansion of the pulmonary lymph drainage can occur over a period of time, and such expansion may occur as a compensatory mechanism for the prevention of overt pulmonary edema.
Release of a Thromboplastic Substance from Arterial Walls by Epinephrine
Authors: SHIMAMOTO TAKIO , ISHIOKA TADAO
Published: June 2012

Aortic preparations of 70 rabbits including the vasa vasorum were perfused in vitro by oxygenated saline under a pressure of 100 mm Hg. The main branches of the aorta were ligated and the perfusate, which irrigates the aortic lumen, but not the vasa vasorum, was sampled every minute. The samples were assayed for thromboplastic activity by means of the calcium clotting time. The calcium clotting time was shortened significantly in samples taken one, two, and three minutes after injection of 0.005 µg epinephrine. The response was present in perfusing with Tyrode's solution as well as with 0.9% NaCl but was absent if oxygen was withheld from the solution. Larger dose of epinephrine (0.05 µg) caused an initial shortening of the calcium clotting time, followed by a prolongation in two out of five cases. Still larger doses (0.5 µg) or much smaller ones (0.0005 µg) were without effect.

In the aortas of rabbits which were pretreated by 5 mg/kg of nialamide two hours before removing the aorta, the previously mentioned effect of epinephrine was prevented. However, direct perfusion of the aortic preparation by a nialamide mixture in vitro did not prevent the release of thromboplastic active substance by epinephrine.

Norepinephrine in doses of 0.005, 0.05, and 0.5 µg was found to be ineffective. These observations may explain the effects of epinephrine on the clotting time of blood originally described by Cannon and Gray.
5
Evidence for Pulmonary Venoconstriction in Brisket Disease
Authors: KUIDA HIROSHI , TSAGARIS THEOFILOS J. , HECHT HANS H.
Published: June 2012

Measurements were made of simultaneous pulmonary artery wedge (PA
w
) and left ventricular diastolic (LV
ed
) pressures 39 times during 21 venous and left ventricular cardiac catheterization studies in eight animals with brisket disease. Each animal was studied during the acute phase of the disease. The remaining 13 studies were carried out in six animals at various intervals during spontaneous recovery from pulmonary hypertension and heart failure. A pressure gradient between PA
w
and LV
ed
(δP) which averaged 14.6 ± 1.6 (SE) mm Hg was demonstrated in 12 measurements during seven studies in four animals (group A). The δP in 27 measurements during 14 studies in six animals averaged 2.4 ±0.8 mm Hg (group B). Venous resistance (R
v
) represented 39±5% of the total resistance (R
T
) of pulmonary vessels in group A and 13±4% in group B studies. The δP and R
v
/R
T
in group A animals are consistent with findings caused by pulmonary venous obstruction. The obstruction was interpreted to represent the effect of pulmonary venoconstriction.
Pressor Effect of Increased Cerebrospinal Fluid Pressure and Vertebral Artery Occlusion With and Without Anesthesia
Authors: DICKINSON C. J. , MCCUBBIN J. W.
Published: June 2012

The intracranial pressures of conscious, lightly anesthetized and fully anesthetized dogs were altered by means of previously implanted intraventricular cannulas, while systemic arterial pressures were simultaneously measured. One vertebral artery was occluded in all these experiments by the catheter used to record aortic pressure. Increased intracranial pressure, which probably acts by reducing cerebral blood flow, caused a rise in systemic arterial pressure whose magnitude depended on the presence and depth of anesthesia. When anesthesia was not used, but when the animals were resting quietly, a significant pressor response occurred within the physiological range of CSF pressure. The response was typically of slow onset, developing over a period of one half to two minutes. It was reproducible, but tended to diminish gradually in the course of several hours if the experiment was continued, although it could be restored if CSF pressure was further increased.

The pulse rate tended to increase slightly, or remain the same, providing CSF pressure was not increased too greatly or too rapidly. Respiratory effects were variable, but most commonly a slightly increased rate and depth of respiration occurred at first, with a return towards normal as the systemic arterial pressure rose.

Similar responses were seen during bilateral artery occlusion, by means of previously implanted inflatable cuffs, in dogs whose carotid sinuses had been excised. These effects were also slow in onset, and were accompanied by comparable respiratory changes. In anesthetized animals with intact carotid arteries, bilateral vertebral artery occlusion produced negligible pressor effects, but was found to augment the response to increased intracranial pressure.

Observations in four dogs with chronic experimental renal hypertension did not reveal notable differences, except that these animals may be less sensitive than normal to increases in intracranial pressure.

The results of these experiments are compatible with the hypothesis that basal systemic arterial pressure during sleep in some degree depends on the cerebrovascular resistance, although it will be important to determine the nature of the slow adaptation seen in these experiments. If this adaptation is brought about by compensatory cerebral vasodilation, this investigation is in accord with the concept of Dickinson and Thomson that some forms of chronic high blood pressure in man might be initiated by cerebral artery occlusion or narrowing of sufficient severity and extent to prevent adequate compensatory vasodilation.
Effect of Changes in Salt Intake on Arterial Pressure and Renal Function in Partially Nephrectomized Dogs
Authors: LANGSTAN JIMMY B. , GUYTOM ARTHUR C. , DOUGLAS B. H. , DORSETT P. E. , Russel Ann , McCaa R. E.
Published: June 2012

Approximately 70% of the total renal tissue was removed in 11 dogs. Control values were then established for mean arterial pressure, urine and plasma sodium concentrations, blood urea nitrogen, glomerular filtration rate, total body weight, and rate of urine formation for these dogs and for two dogs whose kidneys were left intact. Two of the partially nephrectomized dogs were allowed to drink water for the duration of the study while the other animals were required to drink 0.9% sodium chloride solution for various periods of time. The increased salt intake resulted in a 30% to 40% increase in arterial pressure within 48 to 72 hours; plasma sodium concentration increased concomitantly with the development of hypertension. The elevated pressure could be reduced to normal levels within 24 hours by simply allowing the dogs to drink tap water again. Similar results were obtained in a single dog in which renal function had fortuitously been reduced by chronic pyelonephritis.
Carotid and Cerebral Arteriosclerosis in the Rat
Authors: WEXLER BERNARD C. , TRUE CHARLES W. , Beamer Nancy , Conatser Dilman
Published: June 2012

Male and female breeder rats spontaneously develop arteriosclerosis. This occurs first in the aorta and coronary arteries and subsequently in the carotid and intracranial arteries. The carotid arteries show mesenchymal cell proliferation in the media followed by subintimal swelling and mucoid deposition, elastosis, cartilaginous metaplasia and eventual bone formation. Lipid deposition occurs infrequently, and then only in advanced lesions in the media. Severe lesions are much more frequent in the female breeder and the tendency towards cartilaginous metaplasia and bone formation is peculiar to the carotid arteries. The cerebral arteries show little arteriosclerotic involvement except for aneurysm-like outpouchings of the internal elastic membrane associated with mucopolysaccha-ride accumulation about the sites of elastic tissue disruption. Despite severe fulminating arteriosclerosis in the carotid arteries, the cerebral arteries and the brain tissue itself show little or no significant evidence of degenerative change. These results are interpreted to mean that the cerebral arteries of the breeder rat follow a different physiological and morphological pattern of response than the rest of the arterial system.
Non-Newtonian Rheology of Human Blood - Effect of Fibrinogen Deduced by "Subtraction"
Authors: MERRILL EDWARD W. , COKELET GILES C. , BRITTEN ANTHONY , WELLS ROE E.
Published: June 2012

A study of the rheological properties of human blood, from donors in normal health, was carried out by means of a coaxial cylinder viscometer designed to measure very small levels of stress under conditions of "creeping" flow.

It was found that under these conditions of measurement the rheological properties could be conveniently presented by plotting the square root of shear stress against square root of shear rate. For normal blood, a nearly linear relation is found on such a plot, and the intercept on the stress axis at zero shear rate represents the square root of yield stress, separate determination of which is made by other means.

Similar plots for (i) defibrinated blood and (ii) suspensions of red cells in isotonic saline solution reveal no yield stress. Thus it is concluded that fibrinogen is essential for the existence of yield stress in human blood. Furthermore, the approximate linearity, for normal blood, of the square root of shear stress with square root of shear rate, and the yield stress intercept, are of great interest inasmuch as mathematically identical relations ensue according to an equation developed by Casson based on a physical model in which the elementary particles of a suspension are capable of reversible association into rod-like structures, the length of which is controlled by the shear rate. It is of interest to consider the Casson model in the light of rouleaux formation and the relation of fibrinogen to rouleaux formation.
Effect of the Endecapeptide Eledoisin on the Coronary Blood Flow: Comparison with Nitroglycerin, Bradykinin and Epinephrine in the Dog
Authors: BERGAMASCHI MARIO , GLÄSSER ALFREDO H.
Published: June 2012

The effects on coronary blood flow of the endecapeptide Eledoisin have been studied in the anesthetized dog. Eledoisin increases coronary blood flow without increasing myocardial contractility and heart rate. Nitroglycerin and the polypeptide bradykinin increase coronary blood flow in the same way, but are markedly less active than Eledoisin.
l
-Epinephrine increases coronary blood flow, but at the same time produces a stimulating action on the myocardium.
An Experimental Study of the Production and Time Course of Poststenotic Dilatation in the Femoral and Carotid Arteries of Adult Dogs
Authors: Roach Margot R.
Published: June 2012

Three degrees of stenosis were produced in the femoral and carotid arteries of twenty-six adult dogs.
Minimum
stenosis caused neither proximal nor distal dilatation.
Moderate
stenosis, defined by the presence of a distal thrill and bruit, always produced post-stenotic dilatation.
Severe
stenosis, with a marked decrease or absence of distal. pulsation caused temporary proximal dilatation.

The arteries were painted with a radi-opaque paste which did not change their elastic properties and allowed daily measurements of arterial diameter. Radiograms showed that if turbulence was present, the artery usually started to dilate within twenty-four hours, reached a steady state within ten days, and then remained essentially unchanged for up to ten months. The dilatation was fusiform, and usually extended for 1.75 to 2.0 cm distal to the end of the band.

Frequency analysis
of the murmurs showed a wide frequency spectrum with no resonant points and no components over 1500 cycles/ sec. This type of sound is more likely to be produced by turbulence than by cavitation or vortex formation.

Dye injection
in a model showed a random dye distribution starting a short distance distal to the constriction.

Analysis of pressure-volume diagrams from these arteries
35
suggested that the dilatation was due to a weakness of the arterial wall in the poststenotic segment.
Viscosity and Clotting of Blood in Venous Thrombosis and Coronary Occlusions
Authors: DINTENFASS LEOPOLD
Published: June 2012

Viscosity of blood was measured in the absence of anticoagulants by means of an improved cone-in-cone viscometer. Data obtained in a study of a series of patients suffering from venous thrombosis and coronary occlusion were compared with data from a control group of healthy subjects. The probability that the large difference in viscosity observed between normal and abnormal blood is due to chance is approximately 1 in 1,000,000. The viscosity of blood remains constant, at any rate of shear, during the first two to four minutes after removal of blood. Clotting starts after various time periods, depending not only on the intrinsic properties of the particular blood sample, but also on the velocity gradient at which such clotting takes place.

The following general trends were established : at 36°C the onset of clotting is much more rapid at high rates of shear than at low rates of shear. It appears, however, that at lowered temperatures this trend is reversed.

The causes of aggregation of red cells, and the role of this aggregation in clotting, are discussed. It is emphasized that blood is thixotropic, i.e., that its viscosity is both time and rate-of-shear dependent. Thixotropy of blood is due, mainly, to a reversible aggregation of red cells. This suggests the existence of intermittent sedimentation of red cell aggregates during flow in blood vessels. Owing to the existence of a velocity profile, in which the axial region is under zero or near-zero rate of shear, such aggregates should be present especially in large veins and arteries. It appears that an increased thixotropy and viscosity are symptomatic of some thrombotic states.
An Extra-Adrenal Factor Essential for Chronic Renal Sodium Retention in Presence of Increased Sodium-Retaining Hormone
Authors: DAVIS JAMES O. , HOLMAN JOHN E. , CARPENTER CHARLES C. J. , URQUHART JOHN , HIGGINS JAMES T.
Published: June 2012

Evidence is presented for an extra-adrenal factor which is necessary for aldosterone or DCA to produce chronic renal Na retention. To study this factor, the left kidney was transplanted to the neck, both adrenal glands and the right kidney were removed and the thoracic inferior vena cava was constricted in six dogs. For a period of two to three weeks, injection of 25 mg/day of DCA resulted in marked Na retention by the transplanted kidney and ascites formed. Neither renal venous hypertension nor the renal nerves were essential for renal Na retention under these circumstances since the transplanted kidney was denervated and its venous drainage was into the external jugular vein with a normal venous pressure. Removal of the caval ligature in four of the dogs was followed by a diuresis and loss of ascites in spite of continued injection of 25 mg/day of DCA. Similar changes occurred during the injection of aldosterone instead of DCA. Measurements of renal hemodynamic function, first, during Na retention and ascites formation and, later, after removal of the caval ligature showed levels of GFR and RPF during Na retention as high as or higher than those observed during the diuresis and subsequent Na balance. In three hypophysectomized dogs with a very low GFR and RPF, Na retention failed to occur during injection of 25 mg/day of DCA. Also, in three adrenalectomized dogs, administration of a large dose of DCA failed to produce chronic Na retention. Finally, four dogs with a large aortic-caval fistula were given 25 mg/day of DCA; sustained Na retention occurred in all four animals and ascites developed in two of the four dogs. A low rate of Na excretion in these animals was present despite a large postprandial rise in GFR. Available evidence indicates that the extra-adrenal factor is either 1) a humoral agent, or 2) some as yet undefined renal functional change.
Spontaneous Coronary Arteriosclerosis in Repeatedly Bred Male and Female Rats
Authors: WEXLER BERNARD C.
Published: June 2012

Repeatedly bred male and female rats of several strains develop arteriosclerosis spontaneously, irrespective of diet. The severity of the lesions differs between male and female breeders. The morphology and pathogenesis of these lesions have been found to be the same in all of the strains examined. Once the process of arteriosclerosis has been initiated within the abdominal aorta, the subendocardial and medium-sized myocardial coronary arteries also show degenerative changes. The large epicardial coronary arteries become arteriosclerotic only when the process of arteriosclerosis has become severe and generally distributed throughout the aorta.

The smaller subendocardial lesions are characterized by occlusive swelling of medial muscle cells and by the presence of vacuoles. These vacuoles react negatively to lipid stains but stain positively for mucopolysaccharide. The myocardial arteries show endothelial hyperplasia, elastosis and accumulations of mucopolysaccharides, especially in the region of fragmented elastic elements. The mucopolysaccharide-rich endothelial cushions eventually become fibrosed. The epicardial arteries show intense accumulations of calcium-mucopolysaccharide complexes. These arteries become greatly distended and can be detected grossly because of their size and tortuosity.

Acute and chronic myocardial infarct-like lesions are found but these cannot be associated with specific coronary thrombi or arteriosclerotic lesions. Valvular scarring, calcification of the papillary muscles and disappearance of myocardial mast cells has been correlated with advancing arteriosclerosis.

The relation between the intensity of coronary arteriosclerosis and the frequency of breeding, the sex of the animal, and the strain indicates that the pathogenesis of this disease in breeder rats is probably governed by hormonal factors, e.g., sex and adrenal steroids, as well as by genetic factors.
Nonuniform Recovery of Excitability in Ventricular Muscle
Authors: HAN JAOK , MOE GORDON K.
Published: June 2012

Recovery of excitability of ventricular muscle was measured at numerous points in exposed dog ventricles at varying distances along six radial axes from a primary point of stimulation. Temporal dispersion of recovery of excitability at various points equidistant from the point of stimulation was minimal after a basic beat but was increased after an early premature beat. The degree of dispersion following a basic beat was increased by stimulation of the cardiac sympathetic nerves, administration of chloroform, ouabain intoxication, administration of higher doses of quinidine, myocardial ischemia, and hypothermia, but it was decreased by administration of sympathomimetic amines.
Multiple Recording During Electrically Induced Atrial Fibrillation
Authors: SANO TOYOMI , SCHER ALLEN M.
Published: June 2012

1. Atrial fibrillation was induced in dogs by single electrical shocks. Close bipolar direct electrograms were taken from various parts of the atrium; as many as 22 electrograms and a standard lead II electrocardiogram were recorded simultaneously. Initial phase and recovery phase of fibrillation were analyzed.

2. In the initial phase of atrial fibrillation, local firing consisting of rapid tachysystole of 996 to 3000 per minute was observed near the stimulating point in most experiments. Except for the leads showing local firing, the interval between beats at each recording point tended to be constant, and a time gap between two successive beats was observed. A propagation pattern could be plotted which seemed to start from the origin of local firing; some beats were conducted only locally, and others (every second, third or fourth discharge) were conducted widely. The cause of atrial fibrillation was considered to be local firing of one small area of the atrium, i.e., the unifocal theory of the origin of atrial fibrillation was supported.

3. During recovery from atrial fibrillation, features similar to those seen in the initial phase often appeared, although local firing disappeared. In some experiments, the atrium was separated electrically into a few groups of cells beating independently, and in others a "circus pathway" appeared to exist in the last beat. It seems that electrical separation of the atrium into many parts and circus movements, or multiple re-entry, may develop during the course of fibrillation, and that these phenomena perpetuate atrial fibrillation.

4. During the last beat of atrial fibrillation, the time required for all cells to depolarize was occasionally less than the duration of the normal sinus beat. A similar phenomenon was sometimes observed in the premature beats following atrial fibrillation.
Myocardial Tension and Oxygen Uptake
Authors: RODBARD SIMON , WILLIAMS CHRISTINE B. , RODBARD DAVID , BERGLUND ERIK
Published: June 2012

Data obtained in 94 tests in nine anesthetized, thoracotomized dogs were re-examined to determine relationships among oxygen uptake per minute (
qO
2
), cardiac frequency (
F
), mean aortic pressure (
P
), stroke volume (
V
), and heart weight (
G
).

Statistical analysis supports the concept that during each systole

qO
2
/G

is empirically related most closely to the peak mechanical tension (
T
) developed by a spherical heart, in accord with the relationship

qO
2
/G-b

/
F
=
aT
, in which
a
and
b
are derived constants for each heart. Peak tension is half the product of the mean pressure and the radius (estimated from the stroke volume).

Myocardial oxygen uptake is viewed as developing through a mechanical positive feedback mechanism which triggers the shortening of contractile elements. The number of such elements triggered in each beat determines the peak tension, the oxygen requirement of that beat, the resulting energy release, and the work. The oxygen costs of tension increase with the size of the heart since tension must be applied throughout the entire surface of each shell of contractile elements. Mechanical efficiency varies with the square of the stroke radius; it is not directly affected by mean aortic pressure or cardiac frequency. Factors affecting the all-or-none phenomenon, mobilization of tension, myocardial efficiency, the law of the heart, myocardial oxygen uptake, and the coronary flow are discussed in light of these findings.
Electrolyte Alterations in Acute Myocardial Ischemic Injury
Authors: JENNINGS ROBERT B. , SOMMERS HERBERT M. , KALTENBACH JOHN P. , WEST JOEL J.
Published: June 2012

The electrolyte shifts occurring in myocardial cells irreversibly injured by ischemia were compared in two groups of dogs; one given 40 minutes of transient ischemia followed by 20, 50, 80, and 200 minutes of restored coronary arterial flow and the other 30, 60, 90, 130, and 240 minutes of permanent ischemia. Each interval of restored arterial flow in the transient ischemia group was associated with marked changes in the electrolyte content of the injured myocardium. Sodium, chloride, and water were increased and potassium and phosphorus were decreased. These changes occurred much more quickly in dogs exposed to transient ischemia than in dogs with comparable periods of permanent ischemia. These data indicate that objective chemical evidence of the death of myocardial cells develops slowly in areas of permanent ischemia primarily because of the reduced flow of blood through the ischemic injured tissue.
Hypersecretion of Aldosterone in Dogs with a Chronic Aortic-caval Fistula and High Output Heart Failure
Authors: DAVIS JAMES O. , URQUHART JOHN , HIGGINS JAMES T. , RUBIN ELLIS C. , HARTROFT PHYLLIS M.
Published: June 2012

Hypersecretion of aldosterone occurred at the onset of signs of congestive heart failure in a large series of dogs with a large infrarenal aortic-caval fistula. There was evidence of right heart failure in all animals and in four of the dogs râles or frank pulmonary edema was present. Marked sodium retention and ascites or edema were consistent findings and in the majority of the animals central venous pressure was elevated.

Hypophysectomy was followed by a striking fall in both aldosterone and corticosterone secretion but in several animals hypersecretion of aldosterone was evident in the absence of the anterior pituitary. Subsequent acute bilateral nephrectomy of these hypophysectomized dogs resulted in a marked drop of aldosterone secretion to a very low level, and a precipitous fall in arterial pressure frequently occurred. An intravenous infusion of a saline extract of each animal's kidneys produced a striking elevation in aldosterone output; corticosterone secretion and arterial pressure increased consistently. The kidneys of these dogs with heart failure secondary to an A-V fistula frequently showed hypergranulation and hyperplasia of the juxtaglomerular cells. The present findings suggest that the increased rate of aldosterone secretion was mediated by the renin-angiotensin system.

Measurements of arterial pressure and renal hemodynamic function demonstrated a fall of mean renal arterial pressure, glomerular filtration rate, and renal plasma flow, whereas arterial pulse pressure above the fistula and presumably in the kidneys was increased. The data suggest that decreased pulse pressure is unnecessary for activation of the renal mechanism leading to hyperaldosteronism.
Electrical Quiescence of Pulmonary Artery Smooth Muscle During Sympathomimetic Stimulation
Authors: SU CHE , BEVAN JOHN A. , URSILLO RICHARD C.
Published: June 2012

Simultaneous recordings of isometric tension and muscle membrane potential have been made in the sympathetic nerve-pulmonary artery preparation of the rabbit. The mean resting membrane potential recorded intracellularly was 51.5 mv. Sympathetic nerve stimulation and
l
-norepinephrine caused contraction without change in the membrane potential and in the absence of action potentials. Increase in extracellular potassium initiated both depolarization and contraction, although these two processes exhibited different latencies and time courses. The significance of these findings is discussed in relation to recent findings of dissociation in smooth muscle between contraction and membrane potential changes.
Influence of a Pyrimidopyrimidine Derivative on Deamination of Adenosine by Blood
Authors: BUNAG RUBEN D. , DOUGLAS C. ROBERTO , IMAI SHOICHI , BERNE ROBERT M.
Published: June 2012

The disappearance of exogenous adenosine from blood is principally due to its degradation into inosine and hypoxanthine by the enzymes present in the erythrocytes. In the presence of intact red cells, Persantin (RA-8 or 2,6-Bis (diethanolamino) -4,8-dipiperidinopyrimido-(5,4-d)-pyrimidine) effectively prevents the disappearance of adenosine. Although Persantin inhibits adenosine deaminase its adenosine-sparing action in whole blood is more likely due to a reduction in permeability of the red cell membrane to adenosine. This property of Persantin makes possible its use as a tool in investigation of the role of adenine nucleotide derivatives in the regulation of the coronary circulation.
Principal Factor Waveforms of the Thoracic QRS Complex
Authors: HORAN LEO G. , FLOWERS NANCY C. , BRODY DANIEL A.
Published: June 2012

High-speed, high-fidelity recordings from 150 to 180 systematically spaced points over the thoracic surface of both a dog and a man have yielded detailed maps of QRS waveforms. With the aid of digital computer analysis, these waveforms have been resolved into the minimum number of mathematically uncorrelated waveforms necessary for adequate resynthesis of all the original QRS complexes. Under the conditions imposed by the experimental design, seven (in the dog) and eight (in the man) such waveforms, or principal factors, were found. Maps were constructed for both the contribution of each principal factor to the various regions of the chest and also for the degree of reproducibility of the original waveforms by successive addition of the principal factors.

The first three factors accounted for an average of 92.8% of the available information on the chest in the dog and 85.4% in the man. A resynthesis of over 99% of the information was achieved for both subjects when all remaining principal factors were also employed. This necessity for more than three factors or generating functions for reproduction of all the known surface potentials was interpreted as strong support to the equivalent multipole concept of the electrocardiographic generator. In addition, the reduction of total surface information into a compact set of waveforms of specified distribution opens an experimental avenue to the examination of such concepts in living subjects.
Pulmonary Capillary Flow Pulse and the Site of Pulmonary Vasoconstriction in the Dog
Authors: MORKIN EUGENE , LEVINE O. ROBERT , FISHMAN ALFRED P.
Published: June 2012

A nitrous oxide-plethysmographic method was used to measure simultaneously the instantaneous pulmonary capillary blood flow and the pressure gradient across the pulmonary vascular bed. The method entailed the use of lightly anesthetized, curarized dogs for the moment-to-moment measurement of nitrous oxide uptake and the corresponding pulmonary arterial and wedge pressures. After establishing the usual patterns of pulmonary capillary blood flow, the flow patterns were modified by atropine, norepinephrine, and acute hypoxia. Before the exhibition of these agents, pulmonary capillary flow was pulsatile, with peak rates of flow of approximately twice the mean. After atropine, the amplitude of the flow pulse decreased passively as stroke volume and the pulmonary arterial pulse pressure decreased. In contrast to atropine, acute hypoxia elicited precapillary vasoconstriction as manifested by an increase in pulmonary arterial pressure and an unchanged pulmonary arterial wedge pressure in conjunction with an unchanged, or diminished and blunted, pulmonary capillary flow pulse. The predominant effect of norepinephrine appeared to be exerted distal to the pulmonary capillary bed since pulmonary arterial and wedge pressures increased in parallel while the capillary flow pulse changed passively according to changes in stroke volume.
Intracellular pH of Rat Atrial Muscle Fibers Measured by Glass Micropipette Electrodes
Authors: LAVALLÉE MARC
Published: June 2012

Measurements of the intracellular pH of mammalian hearts by means of ordinary sealed electrodes are difficult mainly because of the small diameter of most of these muscle fibres. An open-tip pH micro-electrode was designed. The difference between the measurements with this electrode and measurements with a control pyrex glass electrode of the same resistance, filled with the same medium, and immersed in the same solution, is specific for the pH variations of this solution. The new pH electrode, if filled with 0.5
M
KCl, has an electrical resistance of 30 to 100 megohms and a sensitivity of about 30 mv/pH unit. The sensitive head of the device has a diameter of about half a micron and a length of one to two microns. The intracellular pH value of isolated rat atria, beating at 200/min in a Krebs-Ringer solution maintained at 30°C and at a pH value of 7.4, was measured with this method and found to be 6.9.