bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical and Mechanical Responses of Vascular Smooth Muscle to Vasodilator Agents and Vasoactive Polypeptides
Authors: Keatinge William R.
Published: June 2012

Amyl nitrite or sodium nitrite repolarised and relaxed sheep carotid arteries which had been depolarised and contracted by norepinephrine or histamine. These agents had little electrical or mechanical effect on unstimulated arteries. Epinephrine in the presence of phentolamine or Hydergine produced similar effects but the electrical changes were smaller and more variable than with the nitrites. All these agents could cause some relaxation, without electrical changes, of arteries which had been completely depolarised by potassium-rich solution.

Bradykinin and angiotensin, like acetylcholine, depolarised and contracted the arteries even after actions via nerves had been blocked by nicotine and other agents. The effects that they produced when in sustained high concentration were limited in duration. All three agents could contract arteries which were completely depolarised by potassium-rich solution, without any electrical change.

None of these relaxant or stimulant agents had any significant effect at 5°C.

In canine carotid arteries, norepinephrine produced depolarisation and contraction as it does in sheep carotid arteries, but acetylcholine had variable electrical and mechanical effects.

The results suggest that all these vasodilator and vasoconstrictor agents produce their mechanical effects on the arteries partly by changing the cell membrane potential and partly by other means.
Protracted Pressor Response to Angiotensin After Bilateral Nephrectomy in Rats
Authors: Gabelman Edward H. , Rondell Paul A.
Published: June 2012

The pressor response of nephrectomized rats to an injection of renin is marked by a prolonged stable plateau. A similar, prolonged response to angiotensin has been demonstrated and the following aspects of this pressor effect were evaluated.

1. The protracted response was shown not to be due to a persistence of angiotensin in the blood of nephrectomized animals. There are several indications from unrelated studies that angiotensin is destroyed rapidly. Cross-circulation experiments indicate that during the protracted pressor phase blood levels of constrictor materials have fallen to undetectably low levels.

2. No evidence could be obtained to indicate that the neurogenic buffer system is involved in the development of the protracted response. Ganglionic blockade was ineffective in preventing its development.

3. The hemodynamic basis for the response must be a persistent increase in total peripheral resistance (TPR) since there is no increase in cardiac output (CO) in response to the angiotensin infusion. Before infusion, the CO of nephrectomized animals is higher than that of sham-operated control animals.

4. The increase in TPR must be due to an increase in geometric hindrance for no changes in hematocrit or in viscosity result from angiotensin infusion. Blood viscosity is lower in nephrectomized than in sham-operated animals, but this can account for only part of the lower pre-injection control pressure seen in this group.

It appears that in animals depleted of endogenous renin, a large infusion of angiotensin increases vascular resistance by some non-neurogenic, non-humoral mechanism which may represent another type of vascular tone.
Reflex Inhibition of Sympathetic Vasoconstrictor Activity at a Peripheral Locus
Authors: Gebber Gerard Lincoln , Beck Lloyd
Published: June 2012

Section of the lumbar sympathetic chain just proximal to a stimulating electrode most often results in a large increase in the neurogenic constrictor response to stimulation. The increase could not be accounted for by removal of sympathetic discharge present before section, or by an increase in vascular sensitivity to either exogenous or neurogenically released adrenergic amine. The increased neurogenic constriction is attributed to the removal of an inhibition present before nerve section. The inhibitory fibers are distributed over the classic sympathetic outflow and take origin at least in part at a supraspinal level. The inhibition is lost or markedly reduced by hypotension, spinal cord section, spinal anesthesia, section of the preganglionic sympathetics, or by section of the sinus and vagus nerves. The inhibition, lost by sinus and vagus nerve section or by induction of hypotension, can be restored by stimulation of the central ends of the cut nerves and by replacement of blood, respectively. It is concluded that the conventional pressoreceptor reflexes act to inhibit vasoconstrictor tone, at least in part, at a site in the vasoconstrictor pathway peripheral to the spinal cord.
Measurement of Venous Flow by Continuous Thermodilution and its Application to Measurement of Mammary Blood Flow in the Goat
Authors: Linzell James L. , Fleet Ivan R.
Published: June 2012

The thermodilution method of Fegler, previously used as a single injection technique to measure the flow in one of the main veins draining the mammary gland of goats, has been adapted to a continuous injection technique. Saline at room temperature is injected at rates of 10 to 50 ml/min for 20 to 60 sec and the blood flow is calculated directly from the fall in blood temperature downstream. The method has been checked in vivo by cannulation of the vessel and shown to be as accurate as the single injection technique and the measurement of mammary flow on the Fick principle. It is particularly valuable for determining rapidly the proportion of the mammary venous flow leaving by each of the two main veins.
Inhibition of Catecholamine Biosynthesis in Man
Authors: ENGELMAN KARL , SJOERDSMA ALBERT
Published: June 2012

Reduction of catecholamine synthesis by as much as 70% has been achieved in man with the oral administration of a-methyl-para-Ltyrosine, a tyrosine hydroxylase inhibitor. Significant reduction of blood pressure and improvement of the general clinical status have been achieved in patients with pheochromocytoma. However, at the doses employed, no significant blood pressure effects were noted in patients with essential hypertension.
Substitute Adrenergic Transmitters
Authors: CROUT J. RICHARD
Published: June 2012

Substitute, or false, transmitters are compounds which replace norepinephrine (the normal transmitter) in adrenergic nerve endings end which are released by nerve stimulation. Adrenergic function may be depressed by a substitute transmitter if the substitute is less potent than norepinephrine on adrenergic receptors. It is currently believed that methyldopa exerts its antihypertensive effect by this mechanism. Metaraminol may also serve as a substitute transmitter, and the drug can be shown to have antihypertensive properties in man under certain conditions. The antihypertensive effect of monoamine oxidase inhibition may also be mediated by a substitute-transmitter mechanism.
Physical Factors Which Influence Vascular Caliber and Blood Flow
Authors: PETERSON LYSLE H.
Published: June 2012

1. The radii of blood vessels constitute their major biological functions.

2. The radii of blood vessels are abnormally reduced in most forms of hypertension.

3. The radii of blood vessels are determined by distending pressure and by the geometry and stiffness of the wall material. The latter two factors determine the vessel tone. Thus, tone is defined by those factors which determine vessel radius with respect to distending pressure.

4. It is now possible to measure simultaneously the distending pressure and the factors which determine tone, as well as the radius of vessels. Thus, it is possible to quantitate the factors which determine vascular tone: elastic stiffness (E), viscous stiffness (R), radius (r), and wall thickness (8).

5. These factors have been studied in intact dogs, and the tone of the major vessels of the vascular tree has been mapped out.

6. As the vessel wall itself becomes stiffened, compensatory changes may occur in the geometry. As the vessel dilates and thins, the r/8 ratio enlarges, and the vessel becomes relatively more distensible.

7. Little is known about the changes within the vessel wall which are associated with the mechanical properties of the wall, such as smooth muscle, connective tissue, water and electrolyte concentrations and distributions, the nonhomogenous aspects of the tissue components, or the extent of isovolumetric considerations that are applicable.

8. One of the most challenging aspects of cardiovascular research is to define appropriately and measure the factors mentioned above. They certainly represent part of the key to understanding the etiology and development of hypertension.
Inhibition of Adrenergic Activity at a Locus Peripheral to the Brain and Spinal Cord
Authors: BECK LLOYD , DUCHARME DONALD W. , GEBBER GERARD L. , LEVIN JEROME A. , POLLARD ALBERT A.
Published: June 2012

This report confirms that adrenergic discharge can be neurogenically inhibited at a site outside of the central nervous system. Centers controlling peripheral inhibition are located in both the spinal cord and the brain. The inhibition is of the competitive-equilibrium type and can be surmounted by increasing the frequency of lumbar sympathetic stimulation. Inhibition of adrenergic discharge at an extraspinal locus occurs in the dog and in two species of monkey. Confirming evidence for central inhibition of vasomotor activity was also obtained in the cat and dog.

Reflex dilatation can still be obtained after brain transections which abolish all neurogenic tone, confirming that reflex dilatation is in part active, and further showing that the centers that control active reflex dilatation and neurogenic tone can be differentiated by selected lesioning. The pathways in the spinal cord that mediate active reflex dilatation, adrenergic discharge, and inhibition of adrenergic discharge were explored.

Sensitization (loss of accommodation) of pressoreceptors in the carotid sinus of the dog vvas noted within two hours of maintained hypotension. Reaccommodation of pressoreceptors occurred rapidly when the blood pressure was returned to normal. Marked sensitization of the vasomotor center to inhibitory input occurred in the same time period. Deaccommodation to inhibitory input also took place rapidly.
Measurement of Left Ventricular Volume in the Canine Heart by Biplane Angiocardiography: Accuracy of the Method Using Different Model Analogies
Authors: SANMARCO MIGUEL E. , BARTLE STUART H.
Published: June 2012

Casts of the left ventricular cavity were made in 21 canine hearts. Fifty observations were made by means of biplane X-ray films. Left ventricular volume was measured by water displacement and calculated according to six different model analogies. There was good statistical correlation and small error for each of the methods. Method 1, based on the use of the ellipsoid as the reference figure, and using the projected area and the long axis to calculate the transverse diameter, was more accurate than the others. The standard error of estimate with this method was 2.5 ml or approximately 8% at a volume of 30 ml, an average end diastolic volume for a dog weighing 15 kg.
Synthesis of Phospholipid by Foam Cells Isolated from Rabbit Atherosclerotic Lesions
Authors: DAY ALLEN J. , NEWMAN H. A. I. , ZILVERSMIT D. B.
Published: June 2012

In a preliminary study, foam cells from atherosclerotic lesions have been isolated by incubation of the intima with collagenase and elastase. The composition and metabolism of homogeneous preparations of foam cells obtained in this way have been compared with other parts of the atherosclerotic intima. About 1% of the cholesterol and phospholipid of the intima was present in the cells obtained. The phospholipids of the foam cells contained a lower percentage of lecithin and of sphingomyelin and a higher percentage of "phosphatidyl ethanolamine" than the other parts of the intima. The isolated foam cells incubated
in vitro
incorporated P
32
-phosphate into phospholipid at a rate of about 0.5 mµmoles/10
6
cells/hr. The P
32
was incorporated mainly into lecithin and phosphatidyl inositol with smaller amounts incorporated into phosphatidyl ethanolamine, sphingomyelin and lysolecithin.

The amount of P
32
incorporated into phospholipid by the foam cells was compared with that incorporated into phospholipid by other portions of the intima when the aorta was incubated
in vitro
prior to disruption. Up to 6.8% of the phospholipid synthesis was brought about by isolated cells. The significance of the findings in relation to phospholipid synthesis in the atherosclerotic lesion was discussed.
Left Ventricular Ejection in Conscious Dogs:
Authors: NOBLE MARK I. M. , TRENCHARD DIANA , GUZ ABRAHAM
Published: June 2012

Some factors affecting stroke volume were investigated in conscious dogs in which left ventricular outflow was measured with an electromagnetic flowmeter. Stimulation of the heart at constant heart rate, by intracoronary injections of calcium gluconate and isopropylnorepinephrine, or postectopic potentiation failed to produce any increase in stroke volume. By contrast, alterations of posture at constant heart rate with the presumed associated changes in end diastolic dimensions, produced large changes in stroke volume. This resulted from a change in late systolic flow.
Indirect Method for Measurement of Pressure in Blood Capillaries
Authors: INTAGLIETTA M. , ZWEIFACH B. W.
Published: June 2012

The capillary hydrostatic pressure of blood was measured indirectly. We used a microneedle to occlude exposed mesenteric capillaries in rats and frogs without trauma and then determined the motion of the trapped red blood cells that resulted from the absorption or filtration of water through the capillary wall.

The trajectory of red cells was determined from enlarged timed photomicrographs that cover both sides of the occlusion. Gain or loss of water was measured by following the trajectory of two or more red cells to avoid errors due to injury and incomplete occlusion and extrapolating the motion to the instant of occlusion.

Pressures were calculated from Starling's formula for fluid exchange. We assumed that the tissue parameters are an unknown constant in acute preparations; we used available values of filtration coefficients and colloidal osmotic pressures. The results show that 70 to 80% of the capillaries tested lost fluid, and therefore, their blood hydraulic pressure was higher than colloidal osmotic pressure. The pressures calculated in this way were similar to those measured by techniques requiring puncture of the capillary wall. Capillary arteriovenous pressure differences were approximately 4 mm Hg.
Dopamine-Induced Alterations in Left Ventricular Performance
Authors: BLACK WILLIAM L. , ROLETT ELLIS L.
Published: June 2012

Left ventricular responses to dopamine infusion of 1 to 5, 8, and 10 µg/kg per min for 30 minutes were studied in 14 anesthetized intact dogs. Cardiac output (dye dilution) and stroke volume increased progressively while the end diastolic volume (thermodilution) remained constant, signifying more complete ventricular ejection and resulting in a progressive decline in end systolic volume. Heart rate remained unchanged as did aortic mean pressure, but in the presence of a greatly increased systemic blood flow, the calculated peripheral vascular resistance declined progressively. A linear dose-dependent increase in both systolic ejection rate and circumferential shortening rate suggested directionally similar changes in myocardial fiber shortening. Isovolumic contraction was characterized by a marked increase in the peak velocity of left ventricular pressure rise and presumably in the velocity of force generation without change in the maximum pre-ejection force. These results indicate that dopamine increased myocardial contractility. At these infusion doses dopamine differs from norepinephrine and isoproterenol in causing little change in systemic blood pressure or heart rate in the intact dog. The steady heart rate, stable blood pressure, and constant end diastolic volume suggest that the inotropic response to dopamine administration was due to a direct myocardial action which was otherwise unmodified by the preload or afterload of ventricular contraction.
Spontaneous Aortic Lesions in Rabbits II. Relationship to Experimental Atherosclerosis
Authors: SCHENK ERIC A. , GAMAN ELIZABETH , FEIGENBAUM A. S.
Published: June 2012

Lesions in the rabbit aorta that occur spontaneously and contain no lipid consist of intimal mesenchymal proliferation and of medial sclerosis. Although the relationship of diet-induced atheroma to the intimal mesenchymal alterations is still not clear, our experiments have established that (a) the morphologic characteristics of diet-induced atheroma and of the spontaneous medial lesions are dissimilar at all stages of their development, and (b) the presence of spontaneous medial lesions clearly influences the development of atheroma. This influence is related to (a) an increased tendency for atheroma formation at the raised proximal and lateral borders of nodular medial lesions projecting from the luminal surface, (b) the absence of atheroma formation at sites of medial calcification, and (c) a propensity for lipid deposition in areas of acid mucopolysaccharide accumulation within spontaneous medial lesions.
Angiotensin Tachyphylaxis and its Reversal
Authors: KHAIRALLAH PHILIP A. , PAGE IRVINE H. , BUMPUS F. Merlin , TURKER R. Kazim
Published: June 2012

Tachyphylaxis to angiotensin and some analogues has been demonstrated on spirally cut arterial strips from cat, dog, sheep and rat, and on venous strips from rabbit and cat. Rabbit and guinea pig arteries do not appear to become tachyphylactic. A free C-terminal carboxyl group of angiotensin is necessary for binding with receptor sites and development of tachyphylaxis. Tachyphylaxis seems to represent saturation of receptor sites. It can be reversed by plasma fractions rich in angiotensinase A, possibly by metabolizing the N-terminal part of angiotensin directly from the bound state. Dowex 50 can also reverse it, probably by physical adsorption and stronger binding of angiotensin. Angiotensinase A does not metabolize βaspartyl
1
-angiotensin and does not reverse tachyphylaxis to this peptide. A possible scheme of interaction between peptide and receptor site is presented.
Relation of Increase in Muscle Mass to Performance of Hypertrophied Right Ventricle in the Dog
Authors: GEHA ALEXANDER S. , DUFFY JOHN P. , SWAN H. J. C.
Published: June 2012

Right ventricular hypertrophy was produced by chronic constriction (banding) of the pulmonary artery in the dog. Right ventricular muscle mass increased by 40% in 6 to 12 weeks after banding. Maximal work performance of this ventricle also increased; at 12 weeks the mean was 175% more than that of the normal right ventricle.

It was concluded that, per unit of gross myocardial mass, the work performance of the hypertrophied right ventricle of the dog was no less than that of the normal right ventricle.
Prevention of Atherosclerosis in Sub-Human Primates by Chondroitin Sulfate A
Authors: MORRISON LESTER M. , MURATA KATSUMI , QUILLIGAN J. Joseph , SCHJEIDE O. Arne , FREEMAN LEON
Published: June 2012

Sixty-five squirrel monkeys (
Saimiri sciurea
) were studied for a year. During the last 9 months, spontaneously occurring atherosclerosis was accelerated by feeding a diet containing cholesterol and butter. Of six separate groups of animals, three groups were examined for the effects of acid mucopolysaccharides on the process of atherosclerosis. Monkeys treated with parenteral chondroitin sulfate A and fed the cholesterol-butter diet showed statistically significant reductions of serum total lipid levels and aorta lipid levels when compared to control groups on the cholesterol-butter diets. Macroscopic comparison of aortic atherosclerosis showed chondroitin sulfate A-treated animals to have the least atherosclerotic involvement. The acid mucopolysaccharide chondroitin sulfate A may be an effective preventive agent in the treatment of experimentally induced atherosclerosis.
Comparison of the Force-Velocity Relation and the Ventricular Function Curve as Measures of the Contractile State of the Intact Heart
Authors: COVELL JAMES W. , ROSS JOHN , SONNENBLICK EDMUND H. , BRAUNWALD EUGENE
Published: June 2012

The contractile state of the intact canine left ventricle was investigated by determining the instantaneous relations between tension and contractile element velocity (V
CE
) during the course of single, isovolumic beats produced by balloon occlusion of the aorta. The relative sensitivity of this relation was compared with that of the ventricular function curve (VFC) by exerting small inotropic influences. In seven experiments, low doses of norepinephrine always shifted the isovolumic force-velocity (FV) relation, increases occurring in maximum V
CE
(32.7%) and maximum tension (P
0
) (16.9%). The VFC was unchanged in four of the seven dogs. Moderate hypothermia (average 30.8°C) in four dogs increased P
0
(average 28%), with no change, or a fall, in maximum VCE; the VFC during hypothermia was shifted upward and to the left in two experiments and unchanged in two. Moderate increases in heart rate always produced increases in maximum V
CE
(average 13.5%) but no change in the VFC was observed. Thus, the isovolumic FV relation proved more sensitive than the VFC in detecting changes in myocardial contractile state and allowed more complete definition of these alterations by providing separation of changes in shortening velocity from alterations in the strength of myocardial contraction.
Hydraulic Power Associated with Pulmonary Blood Flow and its Relation to Heart Rate
Authors: MILNOR WILLIAM R. , BERGEL DEREK H. , BARGAINER JACK D.
Published: June 2012

Pulmonary vascular input impedance and hydraulic power were measured at various heart rates in 29 anesthetized and 5 unanesthetized dogs. Hydraulic power at the pulmonary veno-atrial junction was measured in 5 dogs. The pulmonary vascular impedance spectrum in the unanesthetized dogs did not differ significantly from that in the anesthetized dogs. Average pulmonary arterial power in the anesthetized dogs was 157 milliwatts (mw), of which 108 mw was associated with mean pressure and flow, and 49 mw with the pulsations around these means. Seventy-eight per cent of this input power was dissipated in passage through the pulmonary bed. Kinetic energy accounted for 7% of the total input power.

Because of a steep fall in impedance between zero and 3 cycles/sec, and a rate-dependent change in the harmonic structure of flow pulsations, there was an inverse relationship between heart rate and the input power for a given mean flow, up to 180 beats/min. Pulmonary vascular dimensions and elasticity, which determine impedance, thus embody a mechanism whereby tachycardia can increase pulmonary blood flow by as much as 35% with an increase in pulmonary arterial input power of less than 5%, without the intervention of vasomotor activity.
Cardiac Malformations in the Rat Induced by Maternal Hypercapnia with Hypoxia
Authors: HARING OLGA M.
Published: June 2012

Forty-seven pregnant rats were exposed for 24 hours to a gas mixture of 6% carbon dioxide, 10% oxygen and 84% nitrogen on different days during gestation. The earliest exposure was on the fifth day after observed copulation, the latest on the sixteenth. The hearts of 370 newborn test rats were studied in serial sections and compared with those from 111 newborn control rats. The over-all incidence of cardiac malformations was 28.1% in the experimental animals and 4.5 % in the controls. In the test groups, severe structural anomalies resulted from exposures as early as the fifth day of gestation.

The results of the present and of previous experiments suggest that maternal hypercapnia in the presence of normal and low oxygen tensions is markedly teratogenic for the cardiovascular system in the rat.
Ventricular Nucleic Acid and Protein Levels with Myocardial Growth and Hypertrophy
Authors: GRIMM ARTHUR F. , KUBOTA RYO , WHITEHORN WILLIAM V.
Published: June 2012

The myocardial DNA, RNA, actomyosin, and total protein concentrations were determined in rat ventricles ranging between 251 and 1635 mg. Three phases of myocardial growth were evident. Phase 1 (ventricular weights less than 550 mg): DNA concentrations remained relatively constant with increasing ventricular weight. The increasing total DNA per ventricle suggests continuing mitotic activity. Phase 2 (ventricular weights between 550 and 1000 mg): total DNA per ventricle remained relatively constant; with ventricular growth there was a progressive decrease in DNA concentrations. This would be the phase of true myocardial hypertrophy. Phase 3: DNA concentrations continued to slowly decrease although the total DNA per ventricle increased. It would appear that this is the result of a renewed synthesis of DNA.

In phases 1 and 2, the RNA concentrations progressively decreased, although the RNA/DNA ratio was increasing. This ratio appeared to reach its maximum value by the end of phase 2 and remain relatively constant in phase 3. Thus in phase 3, the concentrations of DNA and RNA simultaneously decreased to maintain this constant ratio. The ventricular total protein and ventricular actomyosin levels did not change over this range of ventricular weights.
Contractile Activity of Arterioles in the Bat Wing during Intraluminal Pressure Changes
Authors: WIEDEMAN MARY P.
Published: June 2012

Spontaneous contractile activity in the smooth muscle cells that invest arteriolar vessels is widely variable. Arteriolar branches originating from the same parent vessel contract independently of one another with no similarity in frequency or duration of individual contractions.

Direct microscopic observations were made of these vessels in the wing of unanesthetized bats before and after surgical denervation or nerve block by procaine. A major artery of the wing was cannulated and buffered saline was perfused in retrograde fashion to produce periods of increased intra-arterial pressure. Elevation of intraluminal pressure led to enhanced contractile activity both before and after denervation of the vessels. It is concluded that these vessels respond by contraction to increased pressure and that the response is not dependent on nervous activity.
Direct Evidence of Nonuniform Distribution of Vagal Effects on Dog Atria
Authors: NINOMIYA ISHIO
Published: June 2012

The duration of the monophasic action potential (APD), the interval between atrial beats and the delay time between excitation of the right and left atria of dogs were measured, using coaxial suction electrodes, before and during vagal stimulation.

The effect of vagal stimulation on the degree of shortening of APD varied at different recording sites in the atrium, the shortening being more pronounced in the right than in the left atrium. Threshold and rate of recovery after cessation of stimulation varied throughout the atrium. The results indicate that the vagal effect is nonuniformly distributed over the atrium.

The time difference between excitation of the right and left atria increased with vagal stimulation under the present experimental condition, suggesting that a reduction of synchrony of excitation occurred in the atrial myocardial fibers as a whole. The same conclusion was derived from analysis of the pattern of the P wave before and during vagal stimulation.
Effect of Quinidine and Pronethalol on Acetylstrophanthidin-Induced Ventricular Arrhythmia in Cats Treated with Reserpine
Authors: LEVITT BARRIE , ROBERTS JAY
Published: June 2012

With pronethalol, quinidine, and reserpine it was necessary to increase the dose of acetylstrophanthidin which produced arrhythmia in combination with vagal stimulation. However, in reserpine-treated animals, quinidine and pronethalol were ineffective. The capability of large doses of acetylstrophanthidin to produce ventricular arrhythmia was not diminished by quinidine, pronethalol, or reserpine. While pronethalol decreased the S-A nodal rate in normal animals, it failed to produce an effect on rate after reserpine pretreatment. Since after catecholamine depletion by reserpine, pronethalol and quinidine did not affect acetylstrophanthidin-induced ventricular arrhythmia, it is suggested that the antidigitalis effect of these agents is related to their actions to diminish adrenergic nervous activity.
Measurement of Coronary Blood Flow in Dogs with Normal and Abnormal Myocardial Oxygenation and Function
Authors: MOIR THOMAS W.
Published: June 2012

Common left coronary blood flow was measured simultaneously by a recording rotameter and by the Rb
86
chloride clearance method in anesthetized, open chest dogs, and compared over a wide range of flow rates and under conditions of both normal and abnormal myocardial oxygenation and function. Although the Rb
86
clearance method reflected the same directional changes as metered flow, a systematic underestimate was found which ranged from 27% at ischemic flow rates to 54% at hyperemic rates. Myocardial extraction studies supported the view that coronary flow rate and the resultant time that the isotope was in the capillary bed was the major determinant of the underestimate by the Rb
86
method even under conditions of myocardial hypoxia. It was concluded that the Rb
86
method gave an accurate estimate of directional change in coronary blood flow but that the magnitude of the underestimate of actual flow limits its use as a quantitative index.
Influence of Changes in pH on the Mechanical Activity of Cardiac Muscle
Authors: LORKOVIĆ HRVOJE
Published: June 2012

In a comprehensive experimental study, the influence of changes in extra-and intracellular pH on the mechanical and electrical activity of frog heart ventricle preparations has been investigated. The twitch tension and potassium contracture tension were decreased in acid solutions, provided that the concentration of calcium or the frequency of stimulation was low. In solutions with a high calcium concentration, prolonged exposure to acid leads to an increase of the potassium contractures. The electrical activity, measured by intracellular microelectrodes, is abolished in acid solutions if the change of solution in the extracellular space is enforced by perpendicular jet superfusion; with slow perfusion it is well maintained except when [Ca] is high. The lowering of intracellular pH by applying a solution saturated with 80% CO
2
while keeping the extracellular pH constant causes a rapid drop in twitch tension followed by partial recovery. The relaxation phase of single twitches is prolonged and potassium contractures are markedly increased after the high CO
2
has acted for several minutes. When both intra- and extracellular pH are decreased, both twitches and potassium contractures are markedly decreased. The electrical activity is maintained. Some of the effects of variations in pH are discussed in terms of changes in the processes of mechanical activation and inactivation.
Extraction, Purification, and Assay of Human Renin Free of Angiotensinase
Authors: HAAS ERWIN , GOLDBLATT HARRY , GIPSON EDWIN C. , LEWIS LAVERA
Published: June 2012

Three procedures are described for the extraction and purification of renin from 0.05 to 500 g of human kidneys. A uniform yield of renin, free of angiotensinase, resulted from all three procedures.

All tests for renin were carried out in dogs. When more than 10 g of renal tissue was used, renin was determined by the direct method; with smaller amounts, the indirect method, involving the production and the assay of angiotensin, was employed.

Renin substrate free of angiotensinase, suitable for the indirect assay of human renin, was prepared from pooled human serum by a simple procedure.

The angiotensinase-free renin and substrate permitted prolonged incubation for the production of the angiotensin required for the indirect assay. The mean ratio of angiotensin produced (unit per milliter of serum) to the amount of renin added (unit per milliliter of serum) was 1,482 for an 18-hour period of incubation. The large amount of angiotensin produced permitted the indirect assay of minute amounts of human renin (as little as 0.0005 unit, from 5 mg of renal tissue) in the dog. Unless the angiotensinase present in extracts of renal tissue or serum is first removed, the accurate, indirect assay of the renin is not possible.
Failure to Confirm a Prolongation of the Biological Half-life of
22
Na in Hypertensive Patients
Authors: DAHL LEWIS K. , LAX LOUIS C. , YOUNG CHARLES R. , SCHACKOW ECKART , KNUDSEN KNUD D.
Published: June 2012

The biological half-life of
22
Na was measured in 29 patients with uncomplicated essential hypertension and 15 patients with normal blood pressure. All were on a standard regimen with constant diet and known NaCl intake. The biological half-life of
22
Na was found to be similar in those with and without hypertension. This larger series of observations failed to confirm an earlier study from our laboratory in which the biological half-life of
22
Na was reported to be longer in individuals with hypertension. The most likely explanation for the difference is that with the small number of patients studied earlier, there was a fortuitous selection of normotensive subjects with a shorter biological half-life for
22
Na.
Constrction of the Neonatal Aorta by Raised Oxygen Tension
Authors: GILLMAN R. G. , BURTON A. C.
Published: June 2012

A preparation consisting of the great arteries around the heart from neonatal guinea pigs was perfused at constant flow by physiological saline solutions in a bath in which various gases (95% N
2
+ 5% CO
2
, air + 5% CO
2
and 95% O
2
+ 5% CO
2
) were bubbled. The pressure drop across the aorta, including the preductal area, was recorded and the changes in resistance in response to these gas tensions were calculated. The well-known closure of the ductus with increased P
o
2
occurred, but in addition there was a reversible increase, up to 400%, in the resistance of the aortic segment. This was maximal 1 to 2 days after birth, diminishing with age until after 6 days it was very slight. In very young animals (1 to 2 days), responses to air and oxygen were roughly proportional to the P
o
2
. Inspection of injection casts of the vessels showed that the constriction was local in the preductal area, closely resembling that of aortic coarctation. Segments of aorta that did not include the preductal area, and from animals of comparable age, showed very slight constriction to raised P
o
2
. The neonatal vessels of pigs, rabbits and cats showed similar O
2
sensitivity of different degrees, and with different peculiarities as to time lag and repeatability. Neither the ductus nor the neonatal aorta of dogs appears to constrict to increased P
o
2
, and closure of the ductus in this species must be by a different mechanism.

These observations may be interpreted as evidence for the Skodaic theory that infantile aortic coarctation may occur in association and coincident with the closure of the ductus at birth. The administration of high O
2
gases at birth might, in cases of abnormal development, lead to permanent coarctation.
Capillary Filtration in the Small Intestine of the Dog
Authors: JOHNSON PAUL C. , HANSON KENNETH M.
Published: June 2012

The purpose of these studies was to determine the capillary filtration coefficient of the small intestine of anesthetized dogs by the gravimetric technique. Capillary filtration was produced by elevating venous pressure. Filtration rate increased as venous pressure was increased but the relation between the two was not proportional. At venous pressures greater than 10 mm Hg, filtration rate tended to reach a limit. As a consequence, the filtration coefficient decreased at higher pressures. Mean capillary pressure was estimated by the isogravimetric technique. When capillary pressure was 10 mm Hg, the filtration coefficient averaged 0.37 ml/min per 100 g and decreased to 0.11 when capillary pressure was elevated to 20 mm Hg. The reduction in filtration coefficient at high capillary pressures was apparently due to closure of precapillary sphincters.
Norepinephrine Release and Left Ventricular Pressure in the Isolated Heart
Authors: MONROE R. GRIER , LA FARGE C. G. , GAMBLE W. J. , HAMMOND R. P. , MORGAN C. L.
Published: June 2012

In an isolated dog heart, perfused with blood from an anesthetized donor, left ventricular performance was observed during periods in which the left ventricle either contracted isovolumically or was allowed to eject saline. Heart rate and left ventricular end-diastolic pressure were comparable in both. Ventricular performance, as judged by peak systolic ventricular pressure, declined relatively rapidly during isovolumic loading when initial systolic pressures were higher. The efflux of norepinephrine (NE) from the heart was directly related to the systolic pressure of the left ventricle both when the NE concentration of the perfusing blood was normal and when it was reduced to undetectable levels by dialysis. Changes in heart rate did not affect NE efflux nor was NE efflux increased by isobaric loading when the ventricle was distended in diastole without developing pressure in systole. A pathway is described whereby ventricles developing a high systolic pressure may be depleted of NE.
Electrophysiological Effects of Isoproterenol on Purkinje Fibers of the Heart
Authors: KASSEBAUM DONALD G. , VAN DYKE ALAN R.
Published: June 2012

The effects of isoproterenol on resting and action potentials, automaticity and conduction velocity in isolated Purkinje fibers of sheep hearts were studied with microelectrode recording techniques. In quiescent Purkinje fibers, local application of isoproterenol to the site of microelectrode recording caused depolarization to a potential level from which repetitive discharge occurred. During the acceleration in beat frequency, the threshold and maximum diastolic potentials increased. When isoproterenol was applied to the pacemaker of beating fibers, the steepness of the pacemaker potential increased and the rate accelerated. Threshold and maximum diastolic potentials were affected variably in the beating preparation. Isoproterenol did not change conduction velocity in isolated, stimulated Purkinje fibers. The electrophysiological effects of isoproterenol resemble those described previously for epinephrine. The observations do not permit definition of the mechanism of action.
Control of the Activity of Highly Purified Cardiac Actomyosin by Ca
2+
, Na
+
and K
+
Authors: KATZ ARNOLD M. , REPKE DORIS I. , COHEN BARBARA R.
Published: June 2012

The responses of cardiac actomyosin to changes in the concentrations of Ca
2+
, Na
+
and K
+
were examined to evaluate the role that direct actions of these cations could play in the regulation of myocardial contractility. The sensitivity of the Mg
2+
-activated adenosine triphosphatase (ATPase) activity of reconstituted cardiac actomyosin to changing Ca
2+
concentration was similar to that for skeletal actomyosin although both cardiac myosin and actomyosin were less active than the corresponding skeletal proteins at all Ca
2+
concentrations. Activation of both myosins by either the cardiac or skeletal actintropomyosin complex was virtually absent when free Ca
2+
concentration was below 10
-7
M. Full activation was seen at Ca
2+
concentrations greater than 10
-5
M. These findings support the view that variations in intracellular Ca
2+
concentration play a role in regulating myocardial contractility.

Replacement of KCl by NaCl stimulated both the ATPase activity and superprecipitation of cardiac actomyosin. The positive inotropic effects associated with replacement of intracellular K
+
by Na
+
, e.g. the positive staircase accompanying increased heart rate, may therefore be due, in part at least, to a direct action of Na
+
upon the contractile proteins.
Continuous Measurements of Left Ventricular Dimensions in Intact, Unanesthetized Dogs
Authors: RUSHMER ROBERT F. , CRYSTAL DEAN K. , WAGNER CLYDE , ELLIS RlCHARD M. , NASH ALDEN A.
Published: June 2012

Left ventricular dimensions have been directly measured for extended periods of time in intact unanesthetized dogs under various conditions. The diameter of the left ventricle during diastole is very large in relation to the change in diameter during each cycle. Thus, considerable quantities of blood remain within the chamber at the end of systolic ejection. The stroke output can be increased by either more complete systolic ejection during exercise or by greater diastolic filling during a startle reaction. Accelerated heart rate occurs in both cases. Changes in left ventricular diameter occur very rapidly, often being manifest within the duration of a single cardiac cycle. Mechanisms by which changes in ventricular size can be directly affected by neural and hormonal influences are briefly considered.
The Effect of Dihydrocholesterol on the Absorption of Cholesterol by the Rat
Authors: ROSENMAN RAY H. , BYERS SANFORD O. , FRIEDMAN MEYER
Published: June 2012

Simultaneous feeding of dihydrocholesterol and cholesterol to rats significantly reduced the amount of cholesterol absorbed into the thoracic lymph. Hypercholesteremia and hyperphospholipemia developed in rats simultaneously fed cholesterol and cholic acid for 8 weeks. The addition of dihydrocholesterol to this diet also decreased the rate of development and magnitude of the hypercholesteremia, but had no apparent effect upon the rise of plasma phospholipids.
A Tissue Culture Study of the Chick Fibroblast in Relation to Streptococcal Filtrates and Rheumatic Heart Disease
Authors: BOUCEK ROBERT J. , CAMERON GLADYS , SAURINO VINCENT R. , CHAMBERS ROBERT
Published: June 2012

Marked degeneration and disintegration of the chick embryo fibroblast was observed in tissue cultures after their exposure to sera of patients with active or inactive rheumatic heart disease or to the filtrates of beta hemolytic streptococci. Some tissue specificity was demonstrated; sera of the patients or the filtrates of the streptococci failed to affect contractility of the myocardial cells or secretion of the mesonephros. Sera of normal control humans or of patients with other so-called collagen diseases did not seriously affect the fibroblasts. Filtrates of nine other bacteria failed to alter the morphology of the fibroblasts unless severe toxicity was present and the tissue culture died.
Myocardial Function in Severe Hypothermia
Authors: BERNE ROBERT M.
Published: June 2012

The functional status of the myocardium in hypothermia was investigated by means of pulse contours. No evidence for myocardial failure was uncovered on the basis of established criteria. Artificial cardiac acceleration proved to be a dangerous procedure in the hypothermic heart.
The Dynamics of Pulsatile Blood Flow
Authors: PETERSON LYSLE H.
Published: June 2012

The theory of dynamic fluid motion involving the forces manifested by mass, acceleration, viscous friction and vessel wall tension have been considered and studied when arterial blood flow and pressure are pulsatile. These studies and considerations have resulted in the conclusion that arterial blood pressure is dependent upon all of these parameters and that the relationship of pressure and flow is more complex and nonlinear than heretofore generally believed.
Effects of Hypoxia on the Myocardial Metabolism of Intact Dogs
Authors: HACKEL DONALD B. , GOODALE WALTER T. , KLEINERMAN JEROME
Published: June 2012

Coronary blood flow and myocardial oxygen and carbohydrate metabolism were studied in normal intact dogs subjected to different Degreess of hypoxia. Total left ventricular oxygen consumption was maintained during administration of 10 per cent and 5 per cent oxygen owing to increase in coronary flow and myocardial oxygen extraction. Ten per cent oxygen administration had little effect on carbohydrate uptake by the heart. Five per cent oxygen resulted in decreased coefficients of extraction for glucose, lactate and pyruvate, but total utilization was maintained. Complete anoxia resulted in negative arteriovenous differences for lactate and markedly decreased or negative values for pyruvate.
Effect of Growth Hormone upon Body Weight and Incidence of Bacterial Endocarditis in Rats Exposed to Hypoxia
Authors: ROTH FRANKLIN E. , LILLEHEI C. WALTON
Published: June 2012

Somatotropic hormone (STH) administration accelerated the rate of gain of body weight in normal rats, and effectively neutralized the inhibitory effect of hypoxia on gain in body weight. STH administration caused a nonsignificant reduction in the incidence of bacterial endocarditis. STH had no detectable effect upon the usual hypertrophy of the adrenal glands and cardiac ventricles resulting from the stressful exposure. A sex difference was noted in the weight gain response of rats receiving STH.
Limitations of Electric Impedance Plethysmography
Authors: VAN DEN BERG JW. , ALBERTS A. JAPPE
Published: June 2012

Electric impedance plethysmography has been offered as a substitute for mechanical plethysmography and would be particularly suitable for regions in which the mechanical method cannot be applied. A comparative investigation of mechanical and impedance plethysmograms, taken simultaneously from a finger or a forearm, revealed that, while the normal pulsations were reproduced reasonably well, electric impedance plethysmography cannot be employed to determine volume changes following venous occlusion. The reasons are discussed.
The Static Limit of Arterial Blood Pressure in the Dog's Hind Limb
Authors: LEVY MATTHEW N. , PHILLIPS FRED A. , BRIND SHIRLEY H.
Published: June 2012

When the femoral artery is occluded in the anesthetized dog, the pressure in the distal segment usually declines progressively and approaches a static limit asymptotically. This static limit is independent of the original Degrees of vasomotor tone except under extreme conditions. It is concluded that the rapid supervention of reactive hyperemia in the dog vitiates the static limit as an index of vasomotor tone, unless an instantaneous method is developed for its estimation.
Hyperlipemia and Atheromatosis in a Hibernator,
Citellus columbianus
Authors: BRAGDON JOSEPH H.
Published: June 2012

Ground squirrels occasionally show extreme hyperlipemia. Triglycerides predominate, but high levels of cholesterol and phospholipids also occur. Evidence is presented indicating that the hyperlipemia results from periods of dietary caloric excess. During hibernation the triglyceride levels are low. Atheromata were found in the aorta and endocardium in those animals with the highest cholesterol levels.
Determination of Circulating Pulmonary Blood Volume in Dogs by an Arteriovenous Dye Equilibration Method
Authors: RABINOWITZ MURRAY , RAPAPORT ELLIOT , KUIDA HlROSHI , HAYNES FLORENCE W. , DEXTBR LEWIS
Published: June 2012

The "equilibration" method introduced by Bradley to measure circulating "splanchnic blood volume" has been applied to the estimation of "pulmonary blood volume." The theoretic and practical aspects of the method are analyzed. Values for circulating "pulmonary blood volume" determined in anesthetized dogs were not significantly different from values obtained by the "mean circulation time output" method and were significantly greater than those determined by the "slope output" method. When experimental conditions were varied, relatively parallel changes were recorded by the three methods. It is believed that the "equilibration" method is a valid one for estimating circulating "pulmonary blood volume."
Cardiac Metabolism in Experimental Ventricular Fibrillation
Authors: PAUL M. H. , THEILEN E. O. , GREGG D. E. , MARSH J. B. , CASTEN G. G.
Published: June 2012

The cardiac metabolism of the fibrillating left ventricle of the dog heart with and without maintenance of left coronary artery inflow was investigated. During ventricular fibrillation without maintenance of coronary flow, myocardial adenosine triphosphate and glycogen fell progressively, and in vitro oxygen consumption of biopsied tissue initially increased, but with adequate coronary perfusion these elements were maintained. With reinstitution of coronary flow after 30 to 40 minutes of fibrillation without flow, resynthesis of high energy phosphate occurred. The coronary artery-coronary sinus oxygen difference and left ventricular oxygen usage both decreased in the perfused fibrillating heart as compared with the values in the beating heart.