bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of Heart Mitochondria and Glycolytic Metabolism in Experimentally Induced Cardiac Failure
Authors: SCHWARTZ ARNOLD , LEE KWANG SOO
Published: June 2012

Studies were made on the biochemical activity of mitochondria and of homogenates obtained from normal hearts and from hearts after experimentally induced failure. The principal types of failure investigated were: "chronic" congestive failure and acute failure in the guinea pig. The "chronic" failure was induced in from 2 to 10 days by a partial constriction of the ascending aorta, while the acute type of failure was induced by a more severe aortic constriction of a similar type. Various physiological parameters were studied. The "chronic" animals exhibited tachycardia, elevated right ventricular systolic pressure and a significant depression of myocardial contractility. In addition, a highly significant increase in cardiac tissue mass was observed. Passive congestion of the liver, spleen, kidneys, and lungs was evident.

Mitochondria isolated from the hearts of guinea pigs in "chronic" failure exhibited a significant depression of metabolic activity. Thus phosphorylation associated with the oxidation of glutamate, succinate, or α-ketoglutarate was uncoupled in mitochondria isolated from the "failed" heart. Cardiac glycosides administered to animals with experimental cardiac failure did not alter the uncoupled state of the mitochondria, although these agents effected a significant improvement in cardiac contractility. The ATPase activity of the "failed" mitochondria was normal. Experiments concerning the localization of the site or sites of uncoupling of oxidative phosphorylation in the "failed" mitochondria revealed that the defect probably resided in the phosphorylation step associated with the electron transfer between cytochrome C to oxygen.

Homogenates prepared from hearts of chronically failing animals were markedly depressed with respect to oxygen and glucose consumption and lactic acid formation.

Mitochondria isolated from acutely failed guinea pig hearts exhibited a "mild" uncoupling of oxidative phosphorylation manifested as a decrease in responsiveness to a phosphate acceptor system. This was a graded effect, increasing in severity with increasing duration of aortic constriction.

On the basis of the present study, it is possible that uncoupling of oxidative phosphorylation in heart mitochondria may play a role in the development of congestive cardiac failure.
Molecular Form of Theophylline Responsible for Positive Inotropic Activity
Authors: Hardman Harold F.
Published: June 2012

A comparison of the responses of the dog heart-lung, cat papillary muscle and perfused turtle heart preparations to equimolar doses of theophylline and 8-chlorotheophylline indicates that theophylline is a considerably more potent cardiac inotropic agent. This difference in activity has been related to the ionization characteristics of the two drugs. Studies performed on the isolated turtle heart over a pH range of 7.5 to 9.5, in which the ratio of ionized to nonionized theophylline is varied greatly, indicate that positive inotropic activity is determined by the concentration of nonionized theophylline presented to the heart in the perfusion medium. Similar studies with caffeine, which does not ionize to any appreciable degree over this pH range and thus exists almost exclusively in the nonionized form, indicate that positive inotropic activity is also determined by the concentration of nonionized caffeine presented to the heart in the perfusion medium. No significant difference in the positive inotropic activity of these two agents is discernible when they are compared on the basis of equimolar doses of nonionized drug at pH 7.5 and 8.5. No correlation was observed between the concentration of theophylline anion or cation in the extracellular or intracellular aqueous phase and positive isotropic activity over a wide range of drug concentration in the perfused turtle heart. The positive inotropic activity of theophylline and caffeine is influenced by the pH of the perfusion medium when the pH of this solution is less than 7.5. 8-Chlorotheophylline has been shown to be a potent positive inotropic agent, equivalent to theophylline in pharmacological response, when the concentration of nonionized drug is only one-fifteenth that required for an equivalent response from theophylline. The thesis is presented that the nonionized form of theophylline is the active form of the drug at its final site of action as a positive inotropic agent in the perfused turtle heart. It is suggested that a similar conclusion for the activity of this drug in mammalian cardiac tissue should be considered on the basis of the results obtained in the turtle heart and the indirect evidence obtained in mammalian tissues.
Fractional Distribution of Right Ventricular Output in the Lungs of Dogs
Authors: Hamlin Robert L. , Marsland William P. , Smith C. Roger , Sapirstein Leo A.
Published: June 2012

Microspheres, approximately 50 µ in diameter and labeled with scandium
46
, were injected into the jugular vein of seven anesthetized dogs. Each lobe of lung contained nearly equal counts per minute per gram of tissue. This suggests that the indicator was completely mixed with the blood by the time it arrived in the pulmonary artery, and that the perfusion rate of blood per gram of lung is nearly identical for all lobes.
Hypocholesteremic Effect of 17 α-Methyltestosterone in Dogs
Authors: Abell Liese L. , Mosbach Erwin H. , Kendall Forrest E.
Published: June 2012

It has been confirmed that the oral administration of 17 α-methyltestosterone lowers the serum cholesterol concentrations of dogs fed a stock diet containing 3 Gm. of fat and 22 mg. of cholesterol per 100 Gm. The elevated serum cholesterol levels of cholesterol-fed euthyroid dogs, and of hypothyroid dogs fed a high fat diet, were significantly lowered by the oral administration of 17 α-methyltestosterone. The hypocholesteremic effect of 17 α-methyltestosterone was also observed in dogs maintained on a high fat-low cholesterol diet, but not on the same high fat diet supplemented with 1.5 per cent cholesterol. When 17 α-methyltestosterone was given by intramuscular injection in the same dosage as used for oral administration, the hypocholesteremic effect was more rapid and pronounced than that seen following oral administration; 17 α-methyltestosterone consistently lowered the cholesterol content of the α-lipoprotein fraction. Its effect on the β-fraction depended upon the composition of the diet.
Atherosclerosis
Authors: Harman Denham
Published: June 2012

Young, rapidly growing rabbits developed more aortic atherosclerosis on an
ad libitum
cholesterol-containing diet than did older, more slowly growing rabbits. This effect may be due to an affinity of newly formed tissue, produced during growth, for lipids; this may be a partial explanation of the increase in the number of fatty streaks seen around the age of puberty in humans. A possible mechanism, based on local aortic injury, is presented to account for the localization and development of human atherosclerotic lesions.
Chronic Carotid Sinus Compression in Dogs: A Study of Hemodynamic Changes with and without Sinus Denervation
Authors: Little J. Maxwell , Cordell A. Robert , Conrad Eugene A.
Published: June 2012

In two groups of dogs the carotid sinuses were chronically compressed bilaterally by the application of plastic Wakerlin clamps. In the first series of three dogs, the carotid sinus nerves were sectioned and the adjacent vessel walls thoroughly cleaned. Chronic carotid sinus compression resulted in an increase in arterial systolic pressure, diastolic pressure, average arterial pressure, pulse pressure, and heart rate over a period of 422 to 485 days.

In the second series of five dogs, in which the carotid sinus innervation was preserved, chronic carotid sinus compression resulted in a variable but slight change in arterial systolic pressure, a consistent increase in diastolic pressure, a variable but slight change in average arterial pressure--with only one dog showing a consistent significant increase, a consistent decrease in pulse pressure, and a variable effect on heart rate over a period of 593 to 695 days.

The daily administration of 6 Gm. of sodium chloride per day to the second series of dogs resulted in no appreciable changes in pressure. However, there was a tendency for the heart rate to decrease, with three dogs showing a significant decrease. When the salt administration was stopped, the heart rates returned to values near those observed prior to salt administration.

The results suggest that in the first series of dogs, with the carotid sinuses denervated chronically, there is an increase in cardiac output and a decrease in peripheral resistance. In the second series of dogs, with innervation of the sinuses intact and with chronic compression, the results suggest a decrease in cardiac output and an increase in peripheral resistance.
Adrenergic Stimulation of Depolarized Arterial Muscle
Authors: Waugh William H.
Published: June 2012

The excitation-contraction reactions of arterial smooth muscle to epinephrine and electrical current were studied in isolated segments of canine small-caliber arteries by means of a constant-flow perfusion technique. The arterial pressure elevations produced by the contractile responses of the smooth muscle to epinephrine were equally large, reproducible, and specifically antagonized by piperoxan whether or not the artery had been depolarized by isosmotic solutions rich in potassium and devoid of sodium. Responses to electrical current were impaired by potassium depolarization. In the potassium-depolarized vascular smooth muscle, relaxation of the induced contractions was moderately delayed.
Electrical Potential Difference Across Blood Vessels
Authors: Harshaw David H. , Ziskind Howard , Mazlen Roger , Sawyer Philip N.
Published: June 2012

A technique for measuring the potential difference across blood vessel wall in vitro is described. It was found that the potential difference across canine blood vessel wall in vitro is roughly 0 ± 50 µv. under the conditions of this experiment.
Myocardial Function Following Thermal Injury
Authors: Merriam Thornton W.
Published: June 2012

Several investigators have suggested that a defect in myocardial function occurs in the dog following severe thermal burn. A study was therefore undertaken in which myocardial contractility was measured before and after burn. The left ventricular function curve was used as an index of contractility. Ventricular function was measured immediately before and 30 minutes following 30 per cent body surface area burn in 25 dogs, and before and after a sham burn in 13 control dogs. It was found that the burn produced a significantly greater impairment of myocardial contractility than did the sham burn. The mechanism by which the burn produced this alteration in contractility was not apparent from the results of this study.
In Vivo Incorporation of Acetate-1-C
14
into Cholesterol and Fatty Acids Following Testosterone Propionate Administration
Authors: Raiford Robert L. , Wong Harry Y. c.
Published: June 2012

The administration of testosterone propionate for three weeks resulted in an increased incorporation of sodium acetate-1-C
14
into cholesterol and fatty acids. This increased conversion was evident in both the plain-mash and the atherogenic-diet cockerels. Thus, the hypocholesterolemic effect of testosterone propionate is not the result of a decreased synthesis of cholesterol and/or fatty acids. In addition, a trend towards lowering of the plasma and tissue cholesterol levels of the atherogenic-diet animals is indicated.
Estimation of Left Ventricular Residual Volume in the Dog by a Thermodilution Method
Authors: Rapaport Elliot , Wiegand Bernard D. , Bristow J. David
Published: June 2012

Thermodilution was used to estimate left ventricular volumes by the indicator-dilution principle. The results of multiple determinations in the same animal were in close agreement. Average values determined in 16 dogs anesthetized with a chloralose-urethane mixture were SV 18 ml., ESV 37 ml., EDV 56 ml., and CO 2.54 L./min. The ratio ESV/EDV averaged 66 per cent, which was significantly less than the ESV to EDV ratio of 79 per cent observed in 14 other dogs anesthetized with sodium pentobarbital and studied in a comparable fashion. This difference was attributed primarily to the myocardial depressant effects of the barbiturate anesthetic.

The ability to perform multiple determinations without "indicator" accumulation, to record the time-temperature curve directly at the base of the aorta without sampling through a catheter system, to avoid introducing substances into the circulation which may produce significant circulatory effects, and to perform calibration quickly and easily suggests that the thermodilution technique offers a simple, rapid, and reproducible method for estimating ventricular volumes.
Influence of MER-29 on Experimental Atherosclerosis of Cholesterol-Fed Cockerels
Authors: Wong Harry Y. C. , Johnson Frank B. , farrow francet , Shim ftosa , VonEndt David
Published: June 2012

The effects of MER-29 were studied to determine whether this drug will lower the blood lipids as well as the severity of aortic and coronary atherosclerosis of ten-week-old cockerels on a regimen of plain mash or on an atherogenic diet consisting of 2 per cent cholesterol plus 5 per cent cottonseed oil added to plain mash. After ten weeks of treatment with 12.5 mg. or 25.0 mg. per Kg. of MER-29, it was observed that the drug had no significant influence on the blood cholesterol or phospholipid levels. It was interesting to note that cockerels treated with 25.0 mg. of MER-29 per Kg. body weight, whether on plain mash or on an atherogenic diet, demonstrated an increase of aortic-atherosclerosis. The drug did not seem to lower the incidence of coronary atherosclerosis of the group fed an atherogenic diet. It appears that MER-29 causes aortic atherosclerosis of cockerels fed plain mash primarily by blocking the conversion of 24-dehydrocholesterol to cholesterol, thus increasing the amount of 24-dehydrocholesterol which was found in the aortae, as compared with little or none in the aortae of cockerels on plain mash.
On the Mechanism of Antihypertensive Action of Hydrochlorothiazide in Rats
Authors: Daniel E. E.
Published: June 2012

Hydrochlorothiazide significantly diminishes blood pressure in rats with DCA hypertension. Infusion with hypertonic saline or dextrose failed to reverse the blood pressure effects of hydrochlorothiazide. Infusion of hypotonic saline failed to restore blood pressure to the levels of hypertension in untreated controls in one experiment but tended to do so in another. There was no significant diminution of the inulin space accompanying the hypotensive action of hydrochlorothiazide, nor any relation between the expansion of the extracellular and cardiovascular volumes by various infusions and their effects on blood pressures of thiazide-treated rats. Plasma or extracellular fluid volume alteration was, therefore, not the primary action of hydrochlorothiazide in these rats. Analyses of the composition of plasma, aorta, stomach muscle, psoas muscle, or left ventricle did not support the theory that hydrochlorothiazide acts by decreasing the concentration of intracellular sodium or increasing the ratio of extracellular to intracellular sodium. Changes in composition of the left ventricle suggested that alterations in its function may have influenced some of the blood pressure changes noted. It is suggested that attention should be paid to the action of hydrochlorothiazide on other constituents in vascular and cardiac muscle.
Significance of Immunological Studies in Peripheral Obliterating Vascular Diseases
Authors: Pokorný Josef , Ježkova Zdeňka
Published: June 2012

A statistically significant incidence of antibodies against antigen from normal arteries and blood vessels changed by an atherosclerotic process was found in patients in the acute phase of thromboangiitis obliterans. No such incidence was found in a control group of healthy blood donors and in patients with other diseases. These findings of antibodies can significantly help in the differential diagnosis of the acute phase of thromboangiitis obliterans. It is possible that estimations of antibodies may also be of some value in patients with atherosclerosis obliterans where especially the neutralization test could be important for differential diagnosis of atherosclerosis.
Effect of 2,4 Dinitrophenol on Electrical Activity in Purkinje and Ventricular Muscle Fibers of Hog Heart
Authors: KLEINFELD MORRIS , MAGIN JOHN , MURPHY BERNARD , STEIN EDWARD
Published: June 2012

DNP (2,4 dinitrophenol), in concentrations of 2 to 5 x 10
-5
M produced changes in transmembrane action potential in both the Purkinje and ventricular muscle fibers of the isolated perfused hog heart; however, the time of initiation and rate of change of the different phases of the action potential in the two fibers varied. In the Purkinje fiber, the earliest and most pronounced alteration was a loss in overshoot resulting in a decrease in amplitude of the action potential. Shortly thereafter, the action potential duration shortened, and membrane resting potential decreased. In the ventricular muscle fiber, the earliest and most prominent change was a shortening of action potential duration. This was followed by loss in overshoot and decrease in amplitude of action potential. The membrane resting potential declined but was not significantly different from that noted in Purkinje fiber. The changes in both fibers were reversed completely by washing with Tyrode's solution. The earlier and more pronounced shortening of action potential duration in ventricular muscle fiber as compared to Purkinje is attributed to a greater need of the former for metabolic energy. It may also be conjectured that the greater shortening of action potential duration in ventricular fiber is due to a more marked inhibitory effect of K
+
influx by 2,4 dinitrophenol in this fiber with the K
+
influx coupled to metabolic energy. To account for the more enhanced loss in overshoot in Purkinje fiber, it is suggested that 2,4 dinitrophenol has a greater modifying effect on Purkinje fiber membrane or on its Na
+
carrying system. This results in an earlier and more pronounced decrease in Na
+
influx in this fiber as compared with ventricular muscle fiber.
Properties of Myocardium in Cardiomegaly
Authors: GRIMM ARTHUR F. , KUBOTA RYO , WHITEHORN WILLIAM V.
Published: June 2012

The adult rat's ventricular myocardium is able to increase its mass markedly while maintaining its unit quality. It does so by maintaining constant the design of the sarcomeres: an increase in length is accomplished by the addition of sarcomeres in series; an increase in tension production is accomplished by the addition of more cross-sectional area of a uniform quality. This was shown by the almost constant concentration of the contractile protein, actomyosin, as well as by the histologic evidence of the constancy in the sarcomere lengths. Functional support was obtained by the finding of an identity in the parameters of the length-tension curves; the curves differed only in the absolute magnitude of the tensions, a difference that completely disappeared when suitable corrections were made for the size of the muscle. The electrical parameters also indicated a lack of change in the quality of the excitatory membrane phenomena. However, some data were presented that suggest that the myocardium may show altered properties dependent on the age of the animal. No evidence was found in support of the concept of detrimental consequences at least with this degree of cardiomegaly. It is rather concluded that this degree of cardiomegaly is accomplished without change in the basic architecture, properties, or concentration of the contractile mechanism.
Coronary Blood Flow Measured by I
131
lodo-antipyrine
Authors: KRASNOW NORMAN , LEVINE HERBERT J. , WAGMAN RICHARD J. , GORLIN RICHARD
Published: June 2012

The use of I
131
antipyrine for determining coronary blood flow in intact dogs is described. The correlation with the simultaneous nitrous oxide method was 0.91 ω
m
0.22. Partition coefficient and tissue equilibration were directly determined (1.04 ω 0.13). The method as applied requires only two minutes of sampling and is adaptable to direct writing methods.
Adrenal Cortex and Renal Pressor Function
Authors: SOKABE HIROFUMI , MIKASA AKIRA , YASUDA HISAKAZU , MASSON GEORGES M. C.
Published: June 2012

The pressor response of the nephrectomized rat to the injection of kidney extracts and to a renal graft, was used as an index of the renal content and secretion of pressor substances during adrenal insufficiency or treatment with corticosteroids. Adrenalectomy caused an elevation of both content and secretion, which was best demonstrated after two to three weeks of maintenance therapy. Treatment with cortisone and cortisol decreased slightly but significantly the secretion of pressor substances without altering renal content. ACTH had no effect on either function. Sequential studies of content and secretion of pressor substances during treatment with DCA plus salt showed first a rapid disappearance of prossor activity from renal vein blood followed by a decrease in renal content to near zero levels; DCA without excess salt elicited the same effects but more gradually; administration of 1% saline alone decreased secretion without altering content. It is concluded that salt active corticosteroids specifically inhibit the formation and secretion of renal pressor substances and that determination of the index of secretion constitutes a more reliable and sensitive indicator of the renal pressor function than determination of the pressor activity in kidney extracts.
Nucleic Acid Studies in Experimental Cardiomegaly
Authors: SUMNER ROBERT G. , MCINTOSH HENRY D.
Published: June 2012

1. A group of weanling rats was made anemic by an Fe- and Cu-deficient diet consisting of cow's milk. An appropriate control group receiving Fe and Cu in addition to milk was also studied. After 86-105 days, the rats were sacrificed; hematocrit levels, heart weights, DNA, RNA, and protein concentrations were determined. Total DNA, RNA, and protein contents of the hearts were calculated.

2. Statistical analysis showed a significantly increased mean heart weight, decreased DNA concentration, increased RNA to DNA ratio, and increased total RNA and protein content in the hearts of the anemie group of rats versus the control rats. There were no statistically significant changes in RNA concentration or total DNA content of the hearts.

3. These data are interpreted as showing that the predominant cellular change in cardiae enlargement in the rat with dietary Fe-and Cu-deficiency is that of increase in size of the myocardial cell.
Detection and Measurement of Experimentally Produced Aortic Regurgitation by Means of Indicator-Dilution Curves Recorded from the Left Ventricle
Authors: ARMELIN EGAS , MICHAELS LEON , MARSHALL HIRAM W. , DONALD DAVID E. , CHEESMAN RICHARD J. , WOOD EARL H.
Published: June 2012

In dogs studied without thoracotomy the detection of immediately appearing indicator in the left ventricle following its injection approximately 1 cm downstream from the aortic valve can be used as a reliable index of the presence or absence of aortic regurgitation.

With this type of injection and under the conditions of these experiments, the ratio of the area encompassed by the immediately appearing portion of the dilution curve recorded from the left ventricle to the area encompassed by the primary portion of the curve recorded at the femoral artery bears a close positive correlation (correlation coefficient: 0.9) to the severity of aortic regurgitation as estimated by back perfusion of the valve at necropsy.

Within limitations, the position of the tip of the sampling catheter in the left ventricle in dogs with aortic regurgitation is not an important determinant of the amount of immediately appearing indicator detected in this chamber. Furthermore, although the amount of indicator detected in the left ventricle following injections of very short duration is time-dependent, if the duration of the injection is extended to cover the full systolic or diastolic phase of one heartbeat or continues over one or more heartbeats, the exact timing of this injection in relation to the cardiac cycle is not an important determinant of this variable.

It is concluded that under these conditions the positive correlation established between the amount of immediately appearing dye detected in the left ventricle (expressed as the regurgitant fraction) and the severity of aortic regurgitation determined by back perfusion at necropsy can be used as a valid means of estimating the severity of aoritic regurgitation in dogs.

The applicability of this indicator-dilution method to the study of clinical aortic reguragitation merits further study.
Reflex Control of the Systemic Venous Bed
Authors: BRAUNWALD EUGENE , ROSS JOHN , KAHLER RICHARD L. , GAFFNEY THOMAS E. , GOLDBLATT ALLAN , MASON DEAN T.
Published: June 2012

In a series of investigations on the control of venous tone, it was shown in anesthetized, open-chest dogs on cardiopulmonary bypass that venoconstriction occurs during the infusions of norepinephrine and epinephrine, while trimethaphan results in venodilatation. Lowering the pressure acting on the carotid baroreceptors and on the receptors within the left atrium and left ventricle results in reflex venoconstriction, while stimulation of these receptors relaxes the veins. Hypoxia produces venoconstriction as a result of stimulation of the carotid chemoreceptors, but the veno constriction which results from hypercapnia evidently is primarily central in origin. Reflex venoconstriction to carotid occlusion and central vagal stimulation can be blocked by the administration of guanethidine and reserpine. In intact, unanesthetized human subjects, to whom these drugs were administered orally in doses which are commonly utilized in clinical practice, reflex venoconstriction of the forearm veins was blocked. These investigations emphasize that the systemic venous bed reacts vigorously to neural and humoral stimuli, and that these reactions profoundly alter the cardiac output. In this manner, by exerting control of the rate at which the blood is delivered into the systemic arterial bed, the venous side of the circulation plays an important role in the control of the arterial pressure as well.
Response of the Heart to Increased Peripheral Resistance
Authors: DE MATTOS A. DARWIN , LEVY MATTHEW N. , ZIESKE HARRISON
Published: June 2012

Changes in the resistance to left ventricular outflow were produced in the anesthetized, open-chest dog by constriction of the descending thoracic aorta, the brachiocephalic artery, or a combination of the two. With constriction of the brachiocephalic artery alone, left ventricular stroke work and peak power were considerably enhanced, left atrial pressure increased insignificantly, and cardiac output remained constant. With aortic or combined constriction, cardiac output diminished and left atrial pressure rose, but peak power and stroke work did not change significantly. The enhancement of peak power and stroke work by brachiocephalic constriction may be ascribed in part to the supervention of reflex and humoral inotropic mechanisms.
Effects of Increased Transmural Pressures upon Atrial and Ventricular Rhythms in the Dog Heart-Lung Preparation
Authors: VICK ROBERT L.
Published: June 2012

The effects of increased transmural pressures upon atrial and ventricular rhythms have been studied in the heart-lung preparation of the dog. Increases in right-heart pressure resulted in increased sinus rates when the SA node was intact. When the SA node was crushed and an A-V nodal rhythm revealed, increased right-heart pressure resulted in more rapid A-V nodal rhythms in some preparations while shifts to more rapid pacemakers, adjacent to the SA node, were detected in others. Independent ventricular pacemakers emerged during periods of elevated pressure in every preparation in which the sinus node had been crushed.

Left-heart pressure was increased by augmenting the systemic resistance, the minute volume, or both. In A-V dissociated hearts, epinephrine or metaraminol were administered to enable the generation of higher aortic pressures (above 150 mm Hg). During the periods of elevated pressure, new or increased pacemaker activity was seen in the independently beating ventricle.

These results and others cited show that atrial dilatation or elevated arterial pressure may participate in the genesis of some cardiac arrhythmias.
Influence of Reserpine and βTM 10 on Digitalis-Induced Ventricular Arrhythmia
Authors: Roberts Jay , Ito Ryuta , Reilly Joseph , Cairoli Vincent J.
Published: June 2012

After catecholamine depletion by reserpine, the capacity of the digitalis materials to induce ventricular arrhythmia is diminished. In papillary muscles from cats pretreated with reserpine, the incidence of ouabain-induced extra beats is reduced. The dose of ac. stroph. necessary to induce ventricular arrhythmia in combination with vagal stimulation is increased by reserpine pretreatment. Threshold doses comparable to those in cats not pretreated with reserpine produced arrhythmia after the catecholamine stores were repleted with norepinephrine or isoproterenol.

In dogs with A-V block, βTM 10, an agent which prevents the release of catecholamines, markedly reduces the response of the ventricular pacemaker to ac. stroph.

Since the arrhythmias induced by large doses of ac. stroph. are not affected by reserpine pretreatment, it is concluded that while catecholamine release is the primary mechanism involved in the arrhythmia produced by small doses, another mechanism also plays a role in this action after larger doses.

Only in the dose of 10 mg/kg did it appear that catecholamine depletion did not account entirely for the action of reserpine. The ac. stroph. threshold dose was not increased to the same degree as with the smaller doses of reserpine, and the incidence of ventricular fibrillation induced by the large dose of ac. stroph was reduced.

Hypotension produced by reserpine and βTM 10 did not seem to be an important factor in depression of the responsiveness of the ventricular pacemaker to ac. stroph.

While the incidence of ouabain-induced extra beats was reduced by reserpine pretreatment, the action of ouabain to increase the tension developed by isolated papillary muscles was not affected.
Myocardial Blood Flow and Oxygen Uptake During Acute Red Cell Volume Increments
Authors: Regan Timothy J. , Frank Martin J. , Lehan Patrick H. , Galante James G. , Hellems Harper K.
Published: June 2012

The role of red cell mass in the regulation of coronary blood flow and myocardial oxygen consumption has been examined after acute transfusion of sedimented red cells. Patients with substantial blood-loss anemia had a lower than normal left ventricular oxygen uptake, despite a high myocardial blood flow at rest. A 50% rise of hematocrit reduced coronary flow markedly. Although systemic arterial pressure, cardiac output, and left heart work rose, myocardial oxygen consumption was unchanged.

Red cell transfusion of normovolemic dogs resulted in a decrease of both myocardial flow and oxygen uptake associated with an elevation of time-tension index and left ventricular work, accelerated isometric contraction and prolonged systole. There was no evidence of ischemia or change of left ventricular hemodynamic parameters that would account for the reduced myocardial blood flow and oxygen uptake. These findings, in the presence of an increased oxygen carrying capacity and extraction, would appear to be related principally to enhanced blood viscosity.
Thromboplastic and Fibrinolytic Activities in Vessels of Animals
Authors: ASTRUP TAGE , BULUK KAROL
Published: June 2012

Thromboplastic activity and concentration of plasminogen activator were assayed in the coats of arteries and veins from a number of species. The widely differing patterns found in these species suggest great variation in the tendency to deposit fibrin on the interior surface of the vessels. Several modes of regulating fibrin deposition after intimal injury exist in the animal organism. These observations may assist the evaluation of data obtained in experiments on animals, and they demonstrate certain limitations with respect to conclusions on pathology in man.
Effect of Alterations of Coronary Blood Flow on the Oxygen Consumption of the Nonworking Heart
Authors: Kahler Richard L. , Braunwald Eugene , Kelminson Leslie L. , Kedes Laurence , Chidsey Charles A. , Segal Stanton
Published: June 2012

The effect of varying CBF and myocardial O
2
delivery on MV

O
O2

was studied in 23 experiments. In 14 of the experiments an isolated dog heart was perfused, while in the others the heart of a dog, whose systemic circulation was maintained on cardiopulmonary bypass, was studied. The ventricles were kept empty, developed no pressure and performed no external work, while their temperature was held constant. CBF and myocardial O
2
delivery were controlled by pumping blood into the coronary arteries, total coronary venous return was collected from the right side of the heart and MV

O
O2

, was calculated during a steady state by the Fick principle. Myocardial anoxia was avoided by maintaining the coronary venous O
2
content above 4 vol % and myocardial O
2
extraction below 78%.

A comparison of MV

O
O2

at two levels of CBF (and O
2
delivery) was made in 42 instances, and in 32 of them 11 MV increased substantially as CBF was elevated, or vice versa. The ten exceptions all occurred when O
2
delivery greatly exceeded MV

O
O2

with O
2
extraction ratios below 35%. The fundamental mechanisms responsible for these findings are not clear, but a number of possible explanations are discussed.
Intrinsic Regulation of Skeletal Muscle Blood Flow
Authors: JONES RICHARD D. , BERNE ROBERT M.
Published: June 2012

Isolated, innervated and acutely or chronically denervated resting skeletal muscle of the dog exhibited high intrinsic vascular tone. Sustained alteration of perfusion pressure or venous pressure evoked autoregulatory responses; vascular resistance increased at elevated driving pressures and decreased at reduced driving pressures. Comparable changes of resistance were observed after sustained alteration of blood flow during pump perfusion. Autoregulation was consistently observed during muscle contractions with constant pressure or constant flow perfusion. In resting and contracting skeletal muscle a low venous blood oxygen saturation (VO
2
) was characteristic of preparations exhibiting a high degree of autoregulation. In innervated resting muscle autoregulation was concealed by reflex or local stimuli and its disappearance was associated with a decreased vascular resistance and an increased VO
2
. In resting chronically denervated muscle or in contracting muscle, whether innervated or denervated, such stimuli failed to affect the autoregulatory response. A schema has been proposed to define the "states" of skeletal muscle blood flow and some of the factors responsible for the presence or absence of autoregulation.
Regional Distribution of Glycogen and Phosphorylase in the Ventricles of the Heart
Authors: JEDEIKIN LILLIAN A.
Published: June 2012

In rat, rabbit, dog, and ox hearts, the glycogen concentration varied throughout the walls. The concentration gradient decreased from endocardium to epicardium in the right and left ventricles. In the septum, the interior part of the wall had a lower concentration of glycogen than tissue sections closer to the endocardial surfaces. The maximum values for glycogen concentration in endocardial sections were from two to six times higher than the minimum values. This gradient was much greater than the 30% differences observed between apex and base of the ventricles. Since our studies have demonstrated a very large variation for glycogen content in layers of myocardium parallel to sides of the ventricular wall, there is an obvious need for caution in sampling hearts for glycogen analysis.

In the ox heart, the right bundle branch and A-V node were dissected out, and the glycogen values were compared with those for the rest of the myocardium. Glycogen values of the conduction system, especially of the bundle of His, were considerably higher than for any part of the myocardium studied, indicating that the myocardial gradients observed may be related to distribution of the Purkinje fibers.

Phosphorylase values decreased from endocardium to epicardium in a pattern similar to that observed for glycogen, indicating a possible function in association with glycogen concentration.

In the hearts perfused with a glucose-free medium by the Langendorff technique, glycogen diminished throughout the heart, but the general pattern of gradients was preserved. This suggested that glycogen is utilized as an energy source for contraction.
Variability of Serum Cholesterol Values in Baboons
Authors: STRONG JACK P. , RADELAT PAUL B. , GUIDRY MARION A. , MCMAHAN C. A.
Published: June 2012

Variability of serum cholesterol in baboons was studied in order to obtain estimates of biological and technical variation for use in planning a long term dietary experiment. Variability due to animals, to laboratories, to the day on which blood was drawn, and to laboratory work day was estimated. Implications for the design of experiments involving serum cholesterol in baboons are discussed.
Origin and Conduction of the Mitral Sound in the Heart
Authors: FABER J. JAB
Published: June 2012

Mitral heart sounds were recorded by small microphones inserted in the heart muscles of dogs. Recordings showed that components having frequencies between 20 and 40 cycles/ sec originate at the base of the heart and travel from there to the apex. The velocity of conduction is in the order of 4 m/sec, so that the wavelengths can be calculated to be about 20 to 10 cm. At these frequencies the ventricle seems to vibrate as a whole. Components having frequencies higher than 40 cycles/sec could not be followed during their progression over the heart.

In the range from 20 to 160 cycles/sec, the mitral sounds recorded above and below the mitral valve were of opposite phase so that the mitral valve is the main elastic element responsible for the mitral sound. The combined masses of the heart and the blood in it constitute the inertia of the cardiohemic system. In this range of frequencies oscillations in transmural pressure and circumferential tension of the heart were synchronous and of the same phase.

The low velocity of conduction, the structural similarity between the heart and arteries, and the synchronism in the oscillations of transmural pressure and circumferential tension allow the conclusion that the mitral sound is conducted through the ventricle in the form of a transverse vibration, strictly analogous to the way pulse waves are conducted in arteries.
Adrenergic Effects on Ventricular Vulnerability
Authors: HAN JAOK , DE JALON PERFECTO GARCIA , MOE GORDON K.
Published: June 2012

Effects of stimulation of the cardiac sympathetic nerves and intravenous administration of sympathomimetic amines on the multiple response or fibrillation threshold (VMRT) and on other properties of the dog ventricles were compared. Stimulation of the cardiac sympathetic nerves decreased the VMRT. Administration of sympathomimetic amines caused a brief decrease in the VMRT followed by a sustained increase. Temporal dispersion of recovery of excitability and the degree of ventricular vulnerability were closely related; the ventricle was more vulnerable to fibrillation when the dispersion was increased. The hyperkalemic effect of epinephrine was not responsible for the observed changes in ventricular vulnerability.
Myocardial Mural Thickness During the Cardiac Cycle
Authors: FEIGL ERIC O. , FRY DONALD L.
Published: June 2012

The instantaneous and continuous thickness of the left ventricular wall was measured in ten dogs with a specially designed transducer. The thickness change during the "isovolumic" phase of systole was 11%. The average thickness increased an additional 10% during the ejection period of systole. These average values increased to 20% and 15% respectively with the administration of norepinephrine (approximately 0.001 mg/kg per minute).

Transverse and longitudinal epicardial are strains were compared with thickness strain of the myocardium. Assuming the myocardium is incompressible, reasonable agreement was found in the three strains, which lends support to the measurements that were made.

It is concluded that changes in the thickness of the myocardial wall during the cardiac cycle may be important in some considerations of the heart's performance.
Transmyocardial Temperature Gradient in Dog and Man: Relation to the Polarity of the T wave of the Electrocardiogram
Authors: REYNOLDS ERNEST W. , YU PAUL N.
Published: June 2012

The transmyocardial temperature gradient was measured in both right and left ventricles and in the septum of the dog by percutaneous ventricular puncture, using a no. 21 thin-wall needle fitted with a thermocouple stylus. The outer half of the left ventricular myocardium was invariably warmer than the endocardium. The peak temperature of the right ventricle was located midway between the endocardium and epicardium. The midseptal region was found to have a higher temperature than either its right or left endocardial aspects. The left ventricular cavity was cooler than the right ventricular cavity by a mean of 0.1°C.

The transmyocardial temperature gradient was measured successfully in the left ventricle of two patients with cardiac disease. As in the dog, the outer layers of the myocardium were warmer than either the endocardium or cavity in these two patients. In one patient the T waves in the left precordial leads were negative and in the other the T waves were upright in the same lead.

The location of peak temperature consistently in the outer half of the left ventricular wall may partly explain the normal upright T wave and may contribute to a more rapid recovery in the outer layers of the ventricle compared with the inner layers. However, reversal of the T wave must be explained by other factors and it is apparent that the polarity of the T wave is not governed exclusively by the transmyocardial temperature gradient.

The transmyocardial temperature gradient may be explained partly on the basis of differences in heat removal by blood flow in the coronary system as well as in the ventricular cavity. The latter was found to be an important factor, because during ventricular fibrillation the transmyocardial temperature gradient was abolished.
Measurement of Cardiac Output by Thermodilution with Constant Rate Injection of Indicator
Authors: PÁVEK K. , BOSKA D. , SELECKÝ F. V. , Sauberer A.
Published: June 2012

A mathematical formula has been suggested for measurement of cardiac output by the thermodilution technique using constant rate indicator injection. The theoretical assumptions have been checked in model experiments and in experiments on dogs. The best reproducibility was attained when the indicator was injected into the right atrium, near the tricuspid valve, and the dilution was detected in the pulmonary artery. Recirculation of the cool indicator is negligible and takes place only after the attainment of the curve plateau. No systematic difference was found in simultaneous measurements made by the Fick principle and the injection technique. The correlation coefficient,
r
, was 0.96.
Hemodynamic Changes in Trained Dogs During Experimental Renal Hypertension
Authors: OLMSTED FREDERICK , PAGE IRVINE H.
Published: June 2012

The hemodynamic events, during onset of experimental renal hypertension, and during its progression to the chronic state, were recorded in 19 trained quiet dogs for 20 to 30 minutes daily for four to forty-two days. This was made possible by implanting a flow probe around the root of the aorta, and a catheter in the aortic arch for connection to an external pressure gauge. Continuous graphic recordings of blood pressure, cardiac output, stroke volume, heart rate, and peripheral resistance were made daily during a period of training to obtain control values, and after hypertension was initiated by partial occlusion of a renal artery and unilateral nephrectomy.

The average mean arterial pressure in 34 unanesthetized dogs in this study was 85 mm Hg (range, 68 to 116 mm Hg). This is about 30% below values previously reported by others in unanesthetized dogs. These low pressures were ascribed to lack of restraint, to training, and to the natural posture of the dogs.

At onset of hypertension a sharp rise in arterial pressure was accompanied by a decrease of cardiac output and heart rate, and by a large abrupt increase of peripheral resistance.

After one to four days, the continued rise of arterial pressure was associated with return of cardiac output and heart rate toward normal. Peripheral resistance eventually stabilized at a level above that of the initial large rise. A chronic state of hypertension was reached by ten to twenty days after the initial rise of pressure. At this time cardiac output and heart rate were restored to normal, while peripheral resistance remained elevated. Studies lasting for as long as forty-two days did not show further changes.

If the renal arterial constriction was severe, a third, "malignant" phase ensued with extreme elevation of diastolic pressure, reduction of cardiac output, and greatly increased peripheral resistance. This terminated in uremic death after a few days.
Instantaneous Force-Velocity-Length Determinants in the Contraction of Heart Muscle
Authors: SONNENBLICK EDMUND H.
Published: June 2012

The relations of force and velocity during the course of shortening of heart muscle have been explored using the cat papillary muscle. It has been shown that at any instant during contraction the course of muscle shortening is described by the instantaneous relations of force-velocity and muscle length. The three dimensional force-velocity length diagram allows for greater generalization in the analysis of contraction of heart muscle than has been afforded by the analysis of force and velocity relative to initial muscle length alone, and provides a useful construct for portraying a given contractile state of heart muscle. A change in the velocity coordinate of this diagram (V
max
) with or without a change in the force coordinate (P
o
) serves to define a change in the contractile state of heart muscle.
Estimation of Cardiac Performance and Efficiency During Aortic Occlusion and Induced Muscular Activity
Authors: FRONĚK ARNOŠT , HUDLICKÁ OLGA
Published: June 2012

1) Changes of oxygen uptake and energy output by the left ventricle were investigated during increased peripheral resistance (aortic occlusion) and increased cardiac output (induced muscular activity) in open-chest dogs under pentobarbital anaesthesia.

2) Evidence has been provided to show that energy expenditure during the isovolumic period (
E
1
) participates significantly in the total oxygen consumption of the left ventricle (QO
2
). The correlation of
E
1
+
E
2
(compound energy expenditure during the whole cardiac cycle) to QO
2
was closer than the correlation of the stroke work (
E
2
) to QO
2
under the experimental conditions studied. The increase of QO
2
during increased peripheral resistance is due to a proportional increase of
E
1
.

3) The determination of the total amount of compound energy released by the left ventricle, makes the estimation of the performance of the heart possible in a more specific way. Besides the classical mechanical efficiency, η
m
=
E
2
/QO
2
, an index of the chemomechanical turnover (compound index), i
c
= (
E
1
+
E
2
)/QO
2
), and the so-called pumping index of the left ventricle, i

p

=
E
2
/(
E
1
+
E
2
), have been calculated. During increased peripheral resistance
i

c

did not change while
i
p
decreased, indicating that it is not the index of the chemomechanical turnover but the matching between the heart and the periphery which is impaired. On the other hand, during induced muscular activity, only
i

p

increased, thus indicating an improvement of this matching.