bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrinolytic Activity in Human Atherosclerotic Coronary Arteries
Authors: KWAAN HAU C. , ASTRUP TAGE
Published: June 2012

The localization of fibrinolytic areas in normal and atheromatous human coronary arteries was studied by the histochemical fibrin slide technique. Fibrinolytic activity was caused by a plasminogen activator. The activator, occasionally observed at sites in the normal endothelial lining, was abundantly present in relation to vessels in the normal adventitia. The pathological adventitia contained an increased number of active sites and endothelium covering an atherosclerotic plaque was richer in fibrinolytic sites than the normal endothelium. Within the vascularized plaque, fibrinolytically active capillaries could be traced from their origin in the vasa vasorum or, occasionally, in the endothelium. The results confirm and extend previous observations obtained in assays after extraction. They present patterns similar to those observed in normal tissue repair.
Correlation of Visco-Elastic Properties with Microscopic Structure of Large Arteries
Authors: APTER JULIA T.
Published: June 2012

The media of eight regions of the aorta and three of the pulmonary artery of dogs, as well as isolated elastin, collagen, and smooth muscle obtained from vascular and other sources, were subjected to a step-function circumferential stretch at a variety of temperatures between 0° and 70°C. The tension rose to a peak synchronously with the stretch and then fell along an essentially exponential course to a steady tension. Suitable use of the peak tension, the steady-state tension, and the time required to go from peak to steady state, supplied three temperature-dependent parameters (one viscous and two elastic) characteristic of the material. The two crystalline polymers, collagen and smooth muscle, had higher constants at low temperatures, and the amorphous polymer, elastin, had higher constants at high temperatures. Collagen differed from smooth muscle in its inertness to autonomic drugs and in its elastic modulus. Intact arteries stretched slightly (2% to 20%) in the presence of phenylephrine behaved like smooth muscle; arteries stretched more (20% to 70%) behaved like elastin. At both strain levels, the tensions developed were compatible with in vivo pressures. Arteries stretched even more (> 100%), to tensions compatible with pressures of 300 mm Hg, behaved like collagen.
Analysis of a Recent Hypothesis of Plasma Flow in Pericapillary Spaces
Authors: HOWE JOHN T. , SHEAFFER YVONNE S.
Published: June 2012

The hypothesis that the observed fluid annulus outside the wall of some capillaries is the reservoir of plasma responsible for ratios of organ hematocrit to large vessel hematocrit less than 1 is examined hydrodynamically. The extent to which the hematocrits can be reconciled on the basis of flow through a single capillary is examined. Results show that ratios between 0.5 and 1.0 can be accounted for even if plasma and cells travel the same distance through a common capillary without a plasma annulus. But with the annulus, ratios as low as 0.27 can be explained (ratios as low as 0.35 have been measured), and the corresponding capillary pressure gradients agree better with those cited else-where. The ratio of organ hematocrit to large vessel hematocrit for the heart, lungs, brain, gut, and carcass can be explained on a single capillary basis with or without pericapillary plasma, but that for the liver and kidney requires the plasma annulus.

The analysis predicts a linear relationship between pressure gradient and flow in the capillary with or without the annulus. The hydrodynamic result provides a plasma transit time along the annulus that agrees well with that observed between the "bulk" disappearance and subsequent reappearance of labeled plasma in the microcirculation.
Actin Polymerization and Its Relationship to Adenosine Triphosphatase Activity
Authors: MURTHY VEERARAGHAVAN K. , CREVASSE LAMAR E. , SHIPP JOSEPH C.
Published: June 2012

F-actin was prepared from pig heart myofibrils without the use of organic solvents. G-actin, prepared from F-actin by sonication, had adenosine triphosphatase activity. Dephosphorylation of added ATP by G-actin had a broad pH optimum between pH 7.5 and pH 9.0, specifically required Mg
2+
, and was activated by EGTA. G-actin prepared from skeletal muscle of rabbits by similar methods also showed ATPase activity. Cardiac G-actin and G-actin from skeletal muscle had equimolar nucleotide bound to them. Polymerization of cardiac G-actin was greatest at a pH of about 6.5 and declined above pH 6.8. KCl was necessary for polymerization, and EGTA inhibited the conversion to F-actin. By selectively acetylating G-actin, using acetic anhydride, a preparation of G-actin was obtained that did not have adenosine triphosphatase activity but did polymerize under optimal conditions. It is concluded that dephosphorylation of ATP and the polymerization process in cardiac G-actin are two different reactions occurring at different sites on the actin molecule.
Tachyphylaxis to Alpha- and Beta-Angiotensin in Dogs Perfused with Ringer's Solution or Blood
Authors: LOUIS WILLIAM J. , JERUMS GEORGE
Published: June 2012

Repeated injections of µ-asparaginyl-angiotensin in the hindquarters of dogs perfused either with blood or with Ringer's solution did not lead to tachyphylaxis with doses of less than 0.5 µg. Above this dose tachyphylaxis developed in preparations perfused with Ringer's solution. Tachyphylaxis occurred in blood-perfused preparations at doses of 2 µg and above. Tachyphylaxis to β-aspartyl-angiotensin appeared with doses above 0.5 µg irrespective of the perfusing medium used. It is concluded that plasma angiotensinase activity plays some part in limiting the development of techyphylaxis only to µ-asparaginyl-angiotensin; also, that removal of angiotensin from the biophase is dependent in part on the angiotensin being removed by perfusion. A dynamic model for the action of angiotensin on its receptor is proposed.
Integrity of Energy Stores in Cat Papillary Muscle
Authors: POOL PETER E. , CHANDLER BRIAN M. , SONNENBLICK EDMUND H. , BRAUNWALD EUGENE
Published: June 2012

Although isolated cat papillary muscles have proved useful in a variety of physiologic and pharmacologic studies, the energy integrity of this preparation has been questioned. Accordingly, papillary muscles (avg diam = 1.3 mm) were either placed in oxygenated Krebs solution for 1 hour at 26°C at rest or were made to contract at various frequencies and temperatures and for various durations. In addition, samples of right ventricular muscle were obtained from living cats. Specimens were frozen in liquid nitrogen-cooled isopentane for determination of ATP and creatine phosphate (CP). In vivo CP + ATP of right ventricular muscle was 12.9±0.8 µmoles/g. In papillary muscles at rest, CP + ATP was 16.7±0.6 µmoles/g, significantly higher than right ventricular muscle in vivo (
P
<.01). In vitro at 12 contractions/minute, CP + ATP was 16.0±1.0 µmoles/g, not different from resting papillary muscles but higher than in vivo stores in right ventricular muscle. At 30 or 60 contractions/minute, CP + ATP was reduced to 13.7±1.1 and 11.1±0.7 µmole/g. Neither increasing the in vitro temperature from 26° to 37°C, nor extending the duration of stimulation from 1 to 3 hours at 12/minute significantly altered CP + ATP. It is concluded that the energy stores in papillary muscles, even of moderately large diameter, are intact for at least 3 hours while contracting at frequencies of 12/minute at 26°C. Further, energy stores of papillary muscle are even greater than those found in right ventricular muscle in vivo. While muscle is contracting at 30 or 60/minute, its energy stores may be slightly limited.
Day-to-Day Changes in Coronary Hemodynamics Secondary to Constriction of Circumflex Branch of Left Coronary Artery in Conscious Dogs
Authors: ELLIOT ERIC C. , JONES ELLIS L. , BLOOR COLIN M. , LEON ARTHUR S. , GREGG DONALD E.
Published: June 2012

The studies were carried out in four dogs. The effects of applying ameroid constrictors to the circumflex branch were observed on the circumflex blood flow, circumflex and peripheral circumflex pressures, circumflex reactive hyperemia and aortic-circumflex pressure difference. Recordings were successfully made for periods of 16 to 64 days. During this time the circumflex branch became completely occluded in three of the dogs. The circumflex blood flow remained in the normal range until reactive hyperemia (following a 10- to 12-second occlusion of the circumflex branch) almost disappeared; the flow then decreased to zero in 5 to 10 days. Although there was some rise in mean peripheral circumflex pressure and aortic-circumflex pressure difference before circumflex blood flow decreased, the major rise in these variables occurred only when flow and reactive hyperemia became markedly decreased. The maximum rate of rise of mean peripheral circumflex pressure varied from 6 to 15 mm Hg/24 hours. The experiments indicate that a severe degree of coronary insufficiency precedes a rise in mean peripheral circumflex pressure to 60 to 70 mm Hg. We interpret such increments in mean peripheral circumflex pressure to mean that large collaterals must be open; the studies with injection of Schlesinger mass confirmed this interpretation.
Adrenergic Innervation of the Canine Kidney
Authors: MCKENNA OLIVIA C. , ANGELAKOS EVANGELOS T.
Published: June 2012

The adrenergic innervation of the canine kidney was studied with the fluorescence histochemical method of Falck and Hillarp in conjunction with chemical assays for catecholamines in specific portions of the kidney. Adrenergic nerve fibers were seen traveling along the interlobar, arcuate, and interlobular arteries and along the afferent arterioles. The vasa recta of the outer medulla also received adrenergic innervation. Adrenergic nerve fibers were never seen in association with the glomerulus, the efferent arteriole, or the tubules. The distribution of the nerve fibers agreed with the distribution of norepinephrine. After administration of reserpine or denervation of the kidney, no adrenergic nerve fibers were seen, and the norepinephrine level in all portions of the kidney fell to negligible levels. Accumulation of norepinephrine in the nerve fibers was observed after kidney slices had been exposed to solutions of norepinephrine. On the basis of these experiments, it was concluded that the fibers visualized with the fluorescence histochemical method were adrenergic nerve fibers. The possible physiologic role of the adrenergic innervation of the canine kidney is discussed.
Cardioglobulin
Authors: LEONARD EDWARD J. , MAXIMIN T. J. , HAJDU STEPHEN
Published: June 2012

Two experimental approaches were made to gain insight into the physiological significance of cardioglobulin. The first was to determine whether Cardioglobulin was localized to a particular organ or tissue, since earlier studies had suggested that the system might function as a regulator of myocardial contractility. By fluorescence localization of antibodies to rat cardioglobulin-C, cardioglobulin-C was found not only on the surface of heart muscle cells, but in other extracellular locations which, broadly speaking, were either cell surfaces or basement membrane. The second phase of the study was measurement of plasma activity of cardioglobulin-A, -B, and -C in human diseases. The previously discovered increased overall activity in patients with elevated left ventricular systolic pressure was due to increased cardioglobulin-A. Decreased activity in patients with idiopathic myocardial failure was due to decreased cardioglobulin-C. Patients with advanced cirrhosis and evidence of impaired protein production also had low cardioglobulin-C. Low plasma cardioglobulin was found in 22 of 24 patients with systemic lupus erythematosus. Cardioglobulin was normal in all of 17 patients with other connective tissue diseases. The new tissue and clinical findings may provide a clue in the search for the functional significance of this recently discovered protein system.
Cardiovascular Effects of Griseofulvin
Authors: ALDINGER EARL E.
Published: June 2012

The intravenous administration of griseofulvin in doses of 3.0 mg/kg to 32 anesthetized open-chest dogs produced marked increments (43%) in isometric systolic force measured by a strain gauge. These changes were accompanied by an increase (22%) in heart rate and a decrease (25%) in blood pressure. The effect was unaltered by clamping the blood supply to and from the adrenal glands or by previous treatment with 1 mg/kg reserpine, 0.4 mg/kg propranolol HCl, 10 mg/kg hexamethonium chloride, 1 mg/kg phentolamine HCl or 2 mg/kg atropine. In 11 anesthetized open-chest rats and 7 isolated rabbit hearts, griseofulvin also increased the force of contraction. It may be inferred from these experiments that griseofulvin has a direct action on the cardiovascular system rather than one mediated through neurogenic or hormonal mechanisms. These cardiovascular changes may occur in patients in whom griseofulvin is used in the treatment of fungus diseases.
Sympathetic Vasoconstrictive Responses during Exercise- or Drug-Induced Vasodilatation
Authors: ROWLANDS DEREK J. , DONALD DAVID E.
Published: June 2012

The effect of exercise on the vasoconstrictive response to sympathetic stimulation was studied by observing the changes in perfusion pressure in dogs' hindlimbs perfused at constant flow. During steady-state simulated exercise, a time-dependent increase occurred between 10 and 30 minutes in the magnitude of response to lumbar trunk stimulation or carotid sinus hypotension. This was present (although to a reduced Degrees) in drug-induced vasodilatation and in exercising limbs perfused at constant pressure. The time-dependent change was not due to (1) repetition of stimulus, (2) artifact from muscle electrodes, (3) circulating vasoactive substances, (4) skin circulation, or (5) pH, P
CO
2
, or temperature of the perfusing blood. When norepinephrine was used as the vasoconstrictive stimulus, no time-dependent change was noted. After stabilization, the frequency-response curve of exercising muscle exceeded that at rest at all blood concentrations of norepinephrine and at all save the lowest frequencies of stimulation. It was concluded that vascular smooth muscle can develop greater tension from greater initial length. However, during exercise some factor which operates between the sympathetic nerve ending and the receptor site on vascular smooth muscle initially tends to depress this enhanced ability to develop tension.
Computer Simulation of the Propagation Process in Excitation of the Ventricles
Authors: OKAJIMA MITSUHARU , FUJINO TETSURO , KOBAYASHI TOSHIJI , YAMADA KAZUO
Published: June 2012

Simulation by a digital computer of propagated excitation in the ventricular myocardium has been accomplished. Experience with the program in normal conduction and in one example of abnormal conduction, an extrasystole, is presented. Results of the simulation process were in harmony with observations in animal experiments. This justifies attempts to apply this scheme to the analysis of abnormal ventricular excitation caused by other disturbances.

A crucial role of the Purkinje network in determining the course of excitation spread was recognized in the simulated process of both normal beats and extrasystoles. New knowledge is expected from this scheme when applied to other types of abnormal excitation.

The possibility of combining the scheme with a method of reconstruction of QRS complexes by means of "transfer impedance" values was pointed out.
Increased Monoamine Oxidase Activity during the Development of Cardiac Hypertrophy in the Rat
Authors: DE CHAMPLAIN JACQUES , KRAKOFF LAWRENCE R. , AXELROD JULIUS
Published: June 2012

In rats, the increase in heart mass during normal growth is accompanied by a marked increase in the concentration of monamine oxidase (MAO). Similarly, cardiac hypertrophy resulting from experimental hypertension (induced either by desoxycorticosterone acetate (DOCA) and sodium or by renal artery stenosis) is also associated with a pronounced increase in MAO concentration. Conversely, the delayed growth of the heart occurring during sodium restriction is accompanied by a lower MAO activity. These changes in MAO, independent of the cause, appear closely related to the mass of the heart. However, the reduction in norepinephrine storage observed in the heart and other tissues of rats made hypertensive with DOCA and sodium cannot be explained by the changes in the concentration of MAO. The MAO activity of other tissues of the hypertensive rats is similar to that in the tissues of normal rats, with the exception of the kidney in which the MAO concentration is reduced. The subcellular distribution of MAO is similar in hypertensive and control rats. In both groups, the MAO is mainly localized in the mitochondrial fraction of the liver. In contrast, in the heart, the major fraction of MAO activity is found in the microsomal fraction.
Evidence for Specialized Fibers in the Canine Right Atrium
Authors: HOGAN PERRY M. , DAVIS LARRY D.
Published: June 2012

Right atria from excised beating dog hearts were immersed in Tyrode solution with the endocardial surface of the anterior wall exposed. Glass microelectrodes were used to impale fibers in different anatomical areas of this preparation. Fibers with action potentials similar in contour to those of ventricular Purkinje fibers were found along the caval border of the crista terminalis in the area of the posterior internodal tract. The action potential of these fibers (plateau fibers) had a resting potential of -85 to -95 mv, a sharp spiked overshoot, a long plateau phase, and inherent diastolic depolarization. The maximum velocity of the action potential upstroke of plateau fibers was consistently greater than that of simultaneously recorded fibers which lacked a plateau phase (regular fibers). Epinephrine or isoproterenol produced an increase in both rate and magnitude of diastolic depolarization of plateau fibers and on occasion converted them to true pacemakers. Acetylcholine accelerated repolarization of plateau fibers with disappearance of the plateau. Increases in extracellular concentration of potassium ions from 2.7 to 10.8 mM rendered regular atrial fibers inexcitable, but plateau fibers continued to show action potentials. Plateau atrial fibers possess several characteristics exhibited by specialized conducting and impulse generating fibers. The possibility that these fibers constitute the posterior internodal tract and function in preferential conduction of excitation to the A-V node was discussed.
Dispersion and Attenuation of Small Artificial Pressure Waves in the Canine Aorta
Authors: ANLIKER MAX , HISTAND MICHAEL B. , OGDEN ERIC
Published: June 2012

A method was developed to determine the elastic behavior of large blood vessels in terms of their transmission characteristics for small sinusoidal pressure signals. The method is new insofar as it utilizes transient signals of the form of finite trains of sine waves that are superimposed on the naturally occurring pressure fluctuations and are generated by an electrically driven impactor or by a pump. Its application to the thoracic aortas of 18 mature mongrel dogs anesthetized with pentobarbital has shown that dispersion and attenuation data for frequencies between 40 and 200 cps can be obtained without requiring either Fourier transform computations or resolution of reflection interference. For the frequency range considered, the descending aorta is only mildly dispersive but exhibits strong attenuation that must be attributed primarily to dissipative mechanisms in the vessel wall. At normal blood pressure levels, the wave speed during diastole can have a value between 4 and 6 m/sec. For all frequencies tested the amplitude ratio of the waves exhibits the same exponential decay pattern with distance measured in wavelengths. A marked increase in wave speed observed from diastole to systole can be associated with an increase in mean flow and with a stiffening of the aortic wall due to the rise in pressure. This phenomenon implies that the aortas of anesthetized dogs should exhibit nonlinear properties with respect to large amplitude pulse waves such as those generated by the heart.
Lipid Changes in the Eye Concomitant with the Development of Atherosclerosis in the Aorta in the Rabbit
Authors: ROSCOE HENRY G. , VOGEL ADOLPH W.
Published: June 2012

The lipid changes that occur in the eyes and aortas of male Dutch belted rabbits maintained on 1% dietary cholesterol for 1 to 3 months were studied. In the cornea, iris, ciliary body, and aorta, the most noteworthy lipid change was in tissue cholesterol, which increased with increased time of feeding cholesterol. The phospholipid content of all the tissues increased to a lesser extent but followed the same pattern as cholesterol with respect to time. No changes in tissue triglyceride could be detected during the experimental period. The iris had the capacity to accumulate large amounts of cholesterol. The total iridic tissue (average wet weight, 75 mg/rabbit) accumulated an average of 10.2 mg of cholesterol after the rabbit had eaten a 1% cholesterol diet for 3 months; the average increase was 14.2 mg in aortic tissue (average wet weight = 380 mg/rabbit). The severity of disease graded visually correlated with the cholesterol concentration in the cornea and aorta. Using cholesterol concentration as the criterion, no significant correlation between aortic and corneal disease was found (
P
>0.10), but a good degree of correlation (
P
<0.01) existed between the severity of iridic and aortic involvement over the 3-month experimental period.
Response of Dogs' Cutaneous Veins to Local and Central Temperature Changes
Authors: WEBB-PEPLOE MICHAEL M. , SHEPHERD JOHN T.
Published: June 2012

To study the separate actions of peripheral and central temperature-sensitive systems on the cutaneous veins of the dog, a cross-circulation preparation was made in which hindleg and central temperatures could be varied independently. The lateral saphenous vein of a vascularly isolated hindleg was cross-perfused at constant flow; the difference between perfusion and femoral vein pressures was a measure of venomotor activity. With central temperature constant, local cooling of one leg from 47° to 17°C caused the lateral saphenous vein to constrict; sensitivity to cooling was maximal between 42° and 27°C. With leg temperature constant, central cooling caused the lateral saphenous vein to constrict; over the range of 40° to 33°C, the constriction was linearly related to the decrease in temperature. Central heating reduced the response to local cooling, whereas central cooling had the opposite effect. Thus a decrease in central temperature from 38° to 34°C increased the venoconstrictor response to local cooling from 42° to 22°C by a factor of ten or more.
Reflex Regulation of Arterial Pressure during Sleep in Man
Authors: SMYTH HARLEY S. , SLEIGHT PETER , PICKERING GEORGE W.
Published: June 2012

The control of arterial pressure during sleep was studied in 13 untreated, unsedated subjects aged 20 to 46, including 7 with hypertension. Arterial pressure was measured directly. A transient rise of arterial pressure up to 30 mm Hg was produced by the sudden intravenous injection of 0.25 to 2 µg of angiotensin. Linear plots were obtained in 10 of 13 subjects when the systolic pressures of successive pulses during the pressure rise were plotted against the pulse intervals which began the next beat. The relationship was disturbed by movement or arousal, and was better when pulse intervals falling in inspiration were discarded.

The slope of the line (milliseconds of cardiac slowing per millimeter rise in systolic pressure) in the awake subject ranged from 2 to 15.5 msec/mm Hg, and from 4.5 to 28.9 during sleep. Reflex sensitivity was highest in dreaming sleep. In 7 of 10 subjects, baroreflex sensitivity increased significantly during sleep; in 6, the prevailing arterial pressure was inversely correlated with the baroreflex sensitivity. The pressure appeared to be the dependent variable. It is concluded that the baroreceptor reflex are can be rapidly reset, particularly during sleep. The lower arterial pressures during sleep may be actively maintained in some subjects by increased baroreflex sensitivity.
Effects of Glucagon on Atrioventricular Conduction and Ventricular Automaticity in Dogs
Authors: STEINER CHARLES , WIT ANDREW L. , DAMATO ANTHONY N.
Published: June 2012

The effects of glucagon, 50 µ/kg, on atrioventricular (A-V) conduction and ventricular automaticity were studied in 14 dogs. Atrial pacing was used to control the heart rate. The His bundle electrogram was recorded, and the interval from the pacing impulse (P) to the His bundle spike (H), the P-H interval, was used as a measure of A-V conduction. Ventricular automaticity was estimated in four dogs by recording vagal escape time and idioventricular rate after 60 seconds of continuous vagal stimulation. In three dogs with experimentally produced, complete heart block the effect of glucagon on idioventricular rate was estimated. When the heart rate was 250/minute, glucagon decreased the P-H interval by 30 ± 3%, from 126 ± 5 to 85 ± 5 msec (
P
< 0.01). When the heart rate was 310/minute, eight dogs demonstrated second-degree A-V block before glucagon; after glucagon, seven of the eight showed 1:1 A-V conduction. Glucagon increased heart rate by 38 ± 3.5%, from 148 ± 6.6 to 205 ± 8 beats/min (
P
<0.01). Propranolol, 2 mg/kg, did not block these effects on rate and A-V conduction. The vagal escape time and idioventricular rate with vagal stimulation and idioventricular rate in complete heart block did not change significantly after glucagon. Since glucagon profoundly increased the speed of A-V conduction without increasing ventricular automaticity, it may be useful in the treatment of A-V block especially in the presence of propranolol.
Hepatic Clearance of Renin in Canine Experimental Models for Low- and High-Output Heart Failure
Authors: SCHNEIDER EDWARD G. , Davis James O. , ROBB Charles A. , Baumber John S.
Published: June 2012

Hepatic blood flow, hepatic extraction of renin, and hepatic clearance of renin were compared in normal conscious dogs, in dogs with constriction of the thoracic inferior vena cava (as a model of low-output heart failure), and in dogs with an aortic-caval fistula (high-output heart failure). Both "failure" preparations showed marked sodium retention. Renin was measured by methods described previously and expressed as nanograms of angiotensin produced during incubation per milliliter of plasma. Hepatic plasma flow was determined by the sodium sulfobromophthalein method. The dogs with low-output heart failure had a marked reduction in hepatic plasma flow, while those with high-output failure showed no significant change in this flow. Plasma renin was significantly elevated in both models of heart failure. Dogs with low-output failure had an increase (
P
< .05) in hepatic renin extraction from a normal value of 19.8% to 33.4%, while those with high-output failure showed a decrease in hepatic renin extraction to 11.9% (
P
< .01). The hepatic clearance of renin in low-output failure (104 ml/ min) was the same as the average normal value of 104 ml/min, while clearance of renin by the liver in high-output failure was reduced to 51 ml/min (
P
< .001). The data provide evidence that the decreased metabolism of renin contributes substantially to the increased plasma level of renin in experimental high-output heart failure.
Inhibition of Binding of Tritiated Digoxin to Myocardium by Sodium Depletion in Dogs
Authors: HARRISON CARLOS E. , WAKIM KHALIL G.
Published: June 2012

Ten intact dogs were subjected to hemodialysis against a solution of low-sodium content to determine the influence of sodium depletion on myocardial binding of digoxin-
3
H. Serial determinations of serum sodium, potassium, chloride, bicarbonate, pH, and osmolality, of cardiac output, and of cardiac rhythm were obtained in these and in 10 control dogs dialyzed against the standard solution. A dose of digoxin-
3
H (0.05 mg/kg) was given intravenously after start of the dialysis and the animals were killed 1 hour afterward for measurement of myocardial radioactivity, potassium, and sodium. Significant depletion of serum sodium and chloride and myocardial sodium (
P
< 0.001) occurred in all animals dialyzed against the low-sodium solution. No significant changes occurred in other serum electrolytes or pH; osmolality was maintained constant by a slow intravenous drip of 25% urea or mannitol. Myocardial radioactivity was reduced in sodium-depleted animals by 50% (
P
< 0.001). The Na-K ratio was 0.40 in the myocardium of control animals and 0.26 in sodium-depleted animals. It was concluded that depletion of body sodium inhibits binding of digitalis glycosides to the myocardium during the first hour after injection of the dose.
Relative Roles of Sympathetic and Parasympathetic Nervous Systems in the Carotid Sinus Reflex in Dogs
Authors: BERKOWITZ WALTER D. , SCHERLAG BENJAMIN J. , STEIN EMANUEL , DAMATO ANTHONY N.
Published: June 2012

The effects of electrical stimulation of the carotid sinus on sinus rate and atrioventricular (A-V) conduction were studied before and after alternate interruption of the vagi and sympathetic nerves to the heart in dogs. In group I, carotid sinus stimulation caused a similar absolute decrease in sinus rate before and after vagotomy, although after vagotomy the response was more latent. Subsequent administration of propranolol blocked the effects of carotid sinus stimulation on sinus rate. In group II (dogs with intact vagi), the effects of carotid sinus stimulation and bilateral occlusion of the common carotid artery on sinus rate were abolished by bilateral stellatectomy and upper thoracic ganglionectomy. In group III, the effects of carotid sinus stimulation on A-V conduction during atrial pacing at a fixed rate were not significantly altered by vagotomy and were blocked by subsequent administration of propranolol. In group IV, carotid sinus stimulation had no effect on A-V conduction after sympathetic denervation. It is concluded that the effects of the carotid sinus reflex on the heart are mediated primarily by the sympathetic nervous system efferents. In addition, evidence suggesting that sympathetic tone is a major determinant of vagal tone has been presented.
Association between Autoregulation and Pressure Dependency of Renal Vascular Responsiveness in Dogs
Authors: MCNAY JOHN L. , KISHIMOTO TAKETOSHI
Published: June 2012

We studied the influence of perfusion pressure (arterial pressure minus venous pressure) on the magnitude of responses of renal blood flow to intraarterial injections of acetylcholine, norepinephrine, adenosine, and angiotensin. The left kidney of dogs anesthetized with pentobarbital was denervated, renal arterial flow measured with an electromagnetic flowmeter, and renal perfusion pressure varied by constricting the aorta or renal vein. The percent changes in renal blood flow produced by standardized doses of each vasoactive agent were considered an indication of vascular responsiveness. In kidneys having autoregulation, vascular responsiveness so defined was a function of renal perfusion pressure. In contrast, this correlation was not characteristic of denervated, non-autoregulating canine hindlegs. These experiments do not distinguish between the alternate possibilities that changes in renal vascular responsiveness may have a role in autoregulation or may be a consequence of it.
Dopamine-Induced Alterations in Coronary Hemodynamics in Dogs
Authors: BROOKS HAROLD L. , STEIN PAUL D. , MATSON JAMES L. , HYLAND JOHN W.
Published: June 2012

The effect of intravenous infusions of dopamine on left circumflex coronary blood flow and myocardial oxygen consumption in doses ranging from 5 to 100 µg/kg/min was studied in 17 open-chest dogs anesthetized with chloralose. Flow was measured with an electromagnetic flowmeter. Dopamine caused a progressive and linear increase of coronary flow that was proportional to increases in myocardial oxygen consumption up to a dose of 80 µg/kg/min; at this dose, the increase over control was 365% (28 to 129 ml/min). These changes accompanied marked increases in stroke volume, left ventricular dP/dt, and mean systolic ejection rate. Mean aortic pressure and heart rate changed little at doses below 10 µg/kg/min, but increased steadily with doses over the range of 15 to 40 µg/kg/min.

Dopamine is a potent stimulator of coronary blood flow and myocardial contractility. The fact that the increased coronary flow was proportional to increases in myocardial oxygen consumption indicates that the induced coronary vasodilation is secondary to increased myocardial oxygen demands, rather than the result of primary coronary vasodilation.
Canine Right and Left Ventricular Cell and Sarcomere Lengths after Banding the Pulmonary Artery
Authors: LAKS MICHAEL M. , MORADY FRED , SWAN H.J.C.
Published: June 2012

Canine hearts were fixed with glutaraldehyde at zero transmural pressure 17 to 48 weeks after main pulmonary arterial banding. Tissues were taken from the trabeculae carneae at the ventricular right base, right apex, left base, and left apex. They were placed in osmium tetroxide, embedded in Epon 812, stained with Azure II methylene blue, and sectioned at ½ µ. The mean cell lengths of the hearts with main pulmonary arterial banding were greatest at the right base, 105±5 µ and left base, 103±5.7 µ. (The means ± SE are given.) The mean cell length at the left apex was 95±4 µ and that at the right apex was 92±5 µ. All were greater (P <0.001) than the cell lengths of normal hearts, 71±1.5 µ. The mean sarcomere lengths of the right ventricle with main pulmonary arterial banding (right base, 2.04±0.006 µ right apex, 2.18±0.004 µ) were less than those of normal hearts (right base, 2.41±0.006 µ right apex, 2.46±0.003 µ). The mean sarcomere length of the left base with main pulmonary arterial banding (2.10±0.01 µ) was less than the normal (2.16±0.002 µ); however, the mean sarcomere length of the left apex with main pulmonary arterial banding (2.28±0.005 µ) was the same as the normal.

With main pulmonary arterial banding, both the right and left ventricular cell lengths increased more at the bases than at the apexes, and the sarcomere lengths decreased in the right base, right apex, and left base.
Study of Luminal Coronary Collateral Circulation in the Beating Canine Heart
Authors: MOIR THOMAS W.
Published: June 2012

Coronary collateral circulation from the cardiac lumen was studied in 36 anesthetized, open-chest dogs with hearts beating in situ. The coronary arteries were cannulated and perfused from an isolated, nonradioactive blood source while
131
I-labeled blood circulated through the cardiac lumen for 2 minutes. Ventricular fibrillation was then produced, and luminal blood samples and myocardial tissue samples were obtained for radioactive assay and calculation of the amount of luminal blood appearing as a part of the myocardial blood volume. These volumes were obtained from both ventricles and the atria under (1) normal antegrade coronary flow conditions, (2) myocardial ischemia, (3) left and right ventricular hypertension, and (4) coronary occlusion. Small quantities of luminal blood appeared in the left ventricular myocardium under normal coronary flow conditions while considerably larger amounts were found in the right ventricle and atria. There was no significant increase of the luminal contribution to the myocardial blood volume in response to the various experimental conditions except that of coronary occlusion. Although in the latter, the amount of left ventricular luminal blood was greater than with normal coronary flow conditions, right ventricular and atrial myocardial blood volumes remained greater than the left.
Inadequacy of Perivascular Edema Hypothesis to Account for Distribution of Pulmonary Blood Flow in Lung Edema
Authors: RITCHIE BLAIR C. , SCHAUBERGER GERTRAUD , STAUB NORMAN C.
Published: June 2012

West and co-workers obtained inversion of pulmonary blood flow per unit lung volume (Q
·
/V) in isolated, perfused dog lungs under special pressure-flow conditions in acute edema with high venous pressure. Repeating their experiments, we determined Q
·
/V by the
133
xenon scanning procedure and weighed the lungs continuously to determine the rate of edema formation. Edema slowly developed spontaneously in six lungs in which pulmonary artery pressure exceeded alveolar pressure, which exceeded venous pressure (zone II). We found no Q
·
/V changes. In six other zone II lungs we induced edema rapidly with alloxan. We found no changes in Q
·
/V. In six lungs with high venous pressure in which both pulmonary arterial and venous pressures exceeded alveolar pressure (zone III), we obtained flow inversion when driving pressure was less than 3 mm Hg and blood flow less than 100 ml/min. This confirms West's findings but shows that flow inversion is not related to pulmonary edema in general. We rapidly froze two additional lungs in each set. All showed interstitial perivascular edema, particularly below the hilum. Alveolar walls were more congested and blood vessels more distended at all levels in lungs with high venous pressure than in the other types. We found no vascular compression, kinking, or nipping in lungs showing Q
·
/V inversion. The perivascular spaces of lungs with spontaneous and alloxan-induced edema were distended with fluid, although flow distribution remained normal. We conclude that closure of dependent lung vessels by the accumulation of interstitial perivascular edema is not an adequate explanation for this phenomenon.
Force-Velocity Relationship of Cat Cardiac Muscle, Studied by Isotonic and Quick-Release Techniques
Authors: NOBLE MARK I. , BOWEN T. EARLE , HEFNER LLOYD L.
Published: June 2012

Contractions of isolated cat papillary muscle were studied using a lever system with an electromagnetic load which allowed an on-line computer to control the experiment and to process all the data. Isotonic force-velocity curves were determined in 17 cat papillary muscles; the curves were not hyperbolic. Force-velocity curves at constant time in the contraction and constant contractile element length were obtained with a systolic quick-release technique in 9 muscles. The velocity of shortening after release to low force was almost always less than the maximum recorded following release to slightly higher force. When quick-release force-velocity curves determined at different times in the contraction were compared, the maximum velocity occurred at approximately 60% of the time to peak isometric force. The fall in velocity at lower forces was more marked later in the contraction. The shape of the quick-release force-velocity curves was found to depend on muscle length. At a constant time of release, and ignoring the low force end of the curves, the quick-release force-velocity relationships were not hyperbolic at muscle lengths appreciably below optimum, but near the optimal length the curves were hyperbolic. When these quick-release force-velocity curves were corrected for the presence of an elastic element in parallel with the contractile and series elastic elements, it was found that none of the contractile element force-velocity curves was hyperbolic.
Sympathetic Ganglionic Transmission and the Cardiovascular Changes of the Defense Reaction in the Cat
Authors: BROWN ARTHUR M.
Published: June 2012

The effects of ganglionic blockade on the circulatory components of the defense reaction were studied in 25 anesthetized cats. Hexamethonium alone partially blocked the response; a combination of hexamethonium and atropine was necessary to block it completely. Vasodilation of skeletal muscle was reversed to vasoconstriction during hexamethonium infusion. Direct recording from pre- and postganglionic sympathetic nerves showed persisting ganglionic transmission during hexamethonium infusion that was subsequently blocked by atropine. Unit recordings showed that some ganglion cells were completely blocked by hexamethonium alone. Preganglionic discharge was unaffected. It is suggested that ganglion cells giving rise to cholinergic vasodilator fibers have fewer atropine-sensitive receptor sites than do cells from which adrenergic constrictor fibers arise.
Myocardial Oxygen Metabolism and Myocardial Blood Flow in Dogs in Hemorrhagic Shock
Authors: RATLIFF NORMAN B. , HACKEL DONALD B. , MIKAT EILEEN
Published: June 2012

We have studied the interrelations of myocardial oxygen metabolism and myocardial blood flow in hemorrhagic shock. Myocardial blood flow was measured by the
133
Xe-washout method in closed-chest anesthetized dogs while the dogs were breathing either room air at ambient pressure or oxygen at high pressure. In animals with normal blood pressure, oxygen at high pressure produced a consistent decrease in myocardial blood flow from a mean of 70 ml/100 g/min to a mean of 43 ml/100 g/min, with a proportionate decrease in myocardial O
2
consumption. In animals in hemorrhagic shock, oxygen at high pressure induced no change in myocardial blood flow but increased myocardial O
2
consumption from a mean of 5.9 ml/100 g/min to a mean of 7.4 ml/100 g/min. When the animals in hemorrhagic shock breathed room air again at ambient pressure following oxygen at high pressure, the myocardial blood flow increased from a mean of 40 ml/100 g/min to a mean of 51 ml/100 g/min. The myocardial O
2
consumption did not change. We conclude that with decreasing blood pressure a baseline of myocardial blood flow may be reached, so that a further decrease no longer occurs in response to hyperoxia. However, the control of myocardial blood flow in shock is an active process responsive to complex positive control mechanisms that may be altered and studied experimentally.
Influence of Deformability of Human Red Cells upon Blood Viscosity
Authors: SCHMID-SCHöNBEIN HOLGER , WELLS ROE , GOLDSTONE JERRY
Published: June 2012

The viscosity of blood at high rates of shear is unusually low compared to other suspensions of similar concentration. The underlying mechanisms were studied by rotational viscometry, red cell filtration, viscometry of packed cells and direct microscopic observation of red cells under flow in a transparent cone plate viscometer. Deformability of red cells was altered osmotically or abolished by aldehyde fixation. The normal red cells under isosmotic conditions passed easily through filter pores (5 to 14 µ diameter). After osmotic crenation, deformability of cells in pore flow was reduced. Normal cells were deformed into a variety of shapes at high rates of shear, while crenated cells tumbled undeformed. Suspensions of these normal cells showed more pronounced shear thinning (reduction of viscosity with increasing shear rate) than suspensions of crenated cells. Suspensions of rigid cells showed greatly increased viscosity and a shear thickening as a function of shear rate and shear time. The physiological deformability is of critical importance to blood flow at high rates of shear. This is possible through a fluid transition of the erythrocyte caused by a rotation of the membrane with and around the cell contents. This phenomenon is the prime cause of the progressive reduction in viscosity with increasing shear.
Effect of Altering P-R Interval on the Amplitude of the First Heart Sound in the Anesthetized Dog
Authors: Stept Michael E. , Heid Charles E. , Shaver James A. , Leon Donald F. , Leonard James J.
Published: June 2012

To determine the effect of changing the P-R interval on the intensity of the mitral component of the first heart sound (M
1
amplitude), fixed-rate sequential atrioventricular pacing was used to vary the P-R interval in a steady hemodynamic state in six anesthetized dogs. Left ventricular sound and pressure events were monitored with a catheter-tip micromanometer, and the rate of rise of left ventricular pressure (dP/dt) was recorded using an R/C differentiator. The P-R interval was varied from the longest interval at which continuous ventricular capture was achieved (indifferent P-R interval) to 0.00 msec in 10-msec increments. The mean increase in M
1
amplitude at the short P-R intervals (30 to 50 msec) was 119% compared to the amplitude at the indifferent P-R interval; there was no significant change in maximum dP/dt. No significant changes in left ventricular ejection time and left ventricular peak pressure occurred over the range of P-R intervals. At the indifferent P-R interval, a norepinephrine infusion increased M
1
amplitude 22% and maximum dP/dt 50%. At short P-R intervals in the new inotropic state, the M
1
amplitude was further augmented.

These data indicate that both the timing of atrial and ventricular systoles and the force of left ventricular contraction are major, independent determinants of M
1
amplitude. These findings are consistent with the concept that the abrupt deceleration of blood by the mitral valve shortly after the onset of ventricular systole sets the cardiohemic system into vibration producing the M
1
sound. The intensity of the first heart sound is proportional to the force produced in this manner.
Paradoxical Effect of Vagus Nerve Stimulation on Heart Rate in Dogs
Authors: Levy Matthew N. , Martin Paul J. , Iano Thelma , Zieske Harrison
Published: June 2012

In the anesthetized, open-chest dog, electrical stimulation of the cardiac ends of the transected cervical vagus nerves produced effects on heart rate and A-V transmission that were dependent upon the P-St interval, i.e., the-time from the beginning of the P wave to the beginning of the stimulus. When one vagal stimulus was delivered per cardiac cycle, the pacemaker response curve (curve of the P-P interval as a function of the P-St interval) was sinusoidal in configuration, with a maximum at a P-St interval of 135 msec and a minimum at 349 msec. The mean P-P interval was 568 msec, and the mean amplitude of the pacemaker response curve was 58 msec.

In any given experiment, the range of P-P intervals encompassed by the pacemaker response curve defined a range of frequencies over which S-A nodal rhythm became synchronized with the activity in the vagus nerves. Over such a range, increases in the frequency of vagal stimulation evoked paradoxical increases in heart rate. On either side of this range of synchronization, vagal stimulation elicited pronounced rhythmic oscillations of P-P and P-R intervals. The frequency of such oscillations was equal to the difference between the vagal stimulation frequency and the mean heart rate. The oscillations in P-R interval were approximately 180° out of phase with the oscillations in P-P interval.
Effects of Beta-Receptor Blockade on the Systemic and Coronary Hemodynamic Response to an Increasing Ventricular Rate in the Unanesthetized Dog
Authors: Cobb Fred R. , Bache Robert J. , Ebert Paul A. , Rembert Judith C. , Greenfield Joseph C.
Published: June 2012

Phasic coronary and aortic blood flow and arterial pressure were measured as heart rates were increased by ventricular pacing from 120 to 270 beats/min in unanesthetized dogs before and after beta-receptor blockade with intravenous propranolol. Before beta-receptor blockade, coronary flow progressively increased and coronary vascular resistance decreased with increasing heart rates. Aortic blood flow and arterial pressure were not significantly altered at rates below 240 beats/min. After administration of propranolol, mean coronary blood flow was comparable to that before beta-receptor blockade at heart rates from 120 to 210 beats/min. However, aortic flow progressively decreased and peripheral resistance increased with increasing ventricular rates. At heart rates above 210 beats/min after propranolol coronary vascular resistance increased and coronary flow decreased. These data ascribe considerable importance to beta-receptor activity in the normal hemodynamic adjustments to rapid heart rates.