bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of the A-V Node of the Rabbit to Stimulation of Intracardiac Cholinergic Nerves
Authors: WEST THEODORE C. , TODA NOBORU
Published: June 2012

The cholinergic innervation of the rabbit heart was studied in vitro and in vivo. An isolated preparation, which included the combined atria, S-A node, A-V node and bundle of His, was mounted so that microelectrodes could be placed in either the specialized or nonspecialized tissues. Using a roving monopolar electrode, local transmural electrical stimulation of intracardiac nerves (nerve stimulation) was applied at the A-V or the S-A node. At the A-V node it induced hyperpolarization, reduced the duration and amplitude of action potentials recorded from three regions of the A-V node and the His bundle, whether the preparation was spontaneously beating or electrically driven in either the forward or retrograde direction, and blocked membrane excitation in the nodal and nodal-His regions and to downstream structures. The depressant effects of nerve stimulation were augmented by physostigmine and antagonized by atropine. Addition of acetylcholine to the bath reduced the frequency at which the A-V node conducted, but in the concentrations used did not duplicate the effects of nerve stimulation. The behavior of the S-A node is qualitatively similar to that of the A-V node. In the presence of a sinus rhythm, nerve stimulation applied at the A-V node did not affect the activity of the S-A node, and during artificial atrial drive, nerve stimulation of the S-A node did not affect A-V nodal function, indicating that little or no neural communication exists between the two regions in the isolated preparation. Locally released acetylcholine appears to depress excitability of specialized cells in the central node, independently of the direction of propagation.
Vascular and Extravascular Volumes of the Kidney of Man
Authors: EFFROS RICHARD M. , LOWENSTEIN JEROME , BALDWIN DAVID S. , CHINARD FRANCIS P.
Published: June 2012

Indicator dilution techniques were used to determine the vascular and extravascular volumes of the normal human kidney. Renal volumes were corrected to 1.73 m
2
and refer to one kidney. The renal blood volume (V
IG
) averaged 34.8±3.1 ml; the water contained in the distribution volume of labeled inulin (V
IN
W
) averaged 48.8±9.0 ml, and that of tritiated water (V
THO
W
) 152±20 ml. V
IN
W
was used as an index of the extracellular space of the kidney exclusive of the tubular lumina. V
THO
W
was interpreted to represent the total exchangeable water content of the kidney. The interstitial volume (ΔV
INT
W
) and tubular-cellular volume (ΔV
C
W
) were derived and averaged 27.4±6.2 ml and 93.7±14.3 ml, respectively.

Correction for recirculation by exponential extrapolation was studied and appears satisfactory. Evidence is presented for the existence of significant fluctuations in renal blood flow during the indicator collection intervals, and it is suggested that renal volumes be based on flows determined from the recoveries of each indicator.
On the Cause of Ventricular Asystole during Vagal Stimulation
Authors: VASSALLE MARIO , CARESS DONALD L. , SLOVIN ALVIN J. , STUCKEY JACKSON H.
Published: June 2012

In anesthetized dogs the vagus nerve was stimulated for 2 min; during the first minute the ventricles were driven at a rate higher than the control sinus rate; after discontinuation of the drive, the duration of asystole was prolonged. When the ventricles were driven at a rate lower than the sinus rate during vagal stimulation the subsequent asystole was shortened. Slowing sinus activity by graded vagal stimulation before maximal vagal stimulation led to a shorter asystole. Driving the ventricles at a rate higher than the sinus node rate before vagal stimulation resulted in longer asystole. In animals with chronic atrioventricular block, "overdriving" the ventricles resulted in subsequent temporary inhibition of ventricular pacemakers. In dogs with atrioventricular block, coronary sinus plasma potassium increased during the period of ventricular overdriving, and the magnitude of the rise was a function of the driving rate. These results support the concept that ventricular asystole results from the suppressive action of the fast rate imposed by the sinus node upon the slowly discharging ventricular pacemakers. Suppression of sinus node activity by the vagus reveals the rate-dependent inhibition of ventricular pacemakers. The mechanism of inhibition may be related to changes in ionic concentration gradients.
The Relation of Contractile Enhancement to Action Potential Change in Canine Myocardium
Authors: GREENSPAN KALMAN , EDMANDS ROBERT E. , FISCH CHARLES
Published: June 2012

Simultaneous recordings of contractile tension and transmembrane potentials from canine ventricular tissue yielded a consistent correlation of action potential (AP) alteration with contractile change associated with abrupt rate change. The AP terminating a relative prolongation of the cycle-length manifested shortening of phase 2 with lengthening of phase 3 and was associated with potentiation of contractile force. Conversely, the AP terminating a relative abbreviation of cycle-length displayed a broader phase 2 with a more precipitous phase 3, while the associated contraction was less forceful than the control. In each circumstance, the relative magnitude of cycle-length change correlated with the extent of both AP change and contractile alteration. Changes in AP configuration may reflect changes in transmembrane flux of K
+
during repolarization consistent with the findings of prior workers who have related K
+
efflux to increased contractility. Mechanical alternans, in addition, was frequently observed in association with abrupt rate change and was consistently associated with an electrical alternans manifested by action potentials with alternately wide and narrow plateaus (phase 2). As above, the more forceful contractions were associated with action potentials which displayed a narrower phase 2. Mechanical alternans initiated by abrupt rate change may represent an adaptive phenomenon prior to the establishment of a stable contractile state, as reflected by a stable AP configuration.
Characterization of the Frequency-Force Relationship in the Dog Atrium In Situ
Authors: GRAHAM T. P. , POWELL W. J. , CLANCY R. L. , GILMORE J. P.
Published: June 2012

Isometric developed tension and rate of development of tension in the in situ atrium of the anesthetized dog have been shown to increase consistently with increasing heart rate over a wide range. This study thus definitely demonstrates that both the ascending and descending staircase effects occur in the dog atrium in situ. At high cardiac rates the velocity of force development may increase without a change in the extent of force development. These changes were independent of variations in aortic pressure, intactness of betaadrenergic receptors, level of cardiac catecholamine stores, cardiac innervation, or changes in coronary flow. The character of the frequency-force relationship was found to be markedly influenced by isolation of the heart with its concomitant depression of contractility.
Effect of Respiration on Venous Return and Stroke Volume in Cardiac Tamponade
Authors: GUNTHEROTH WARREN G. , MORGAN BEVERLY C. , MULLINS GAY L. , McGough George A. , Breazeale Donald G.
Published: June 2012

In 40 lightly anesthetized dogs, 5 to 30 days after surgical preparation, flow was measured simultaneously in the venae cavae, pulmonary artery, pulmonary vein, and aorta with ultrasonic flowmeters. Intrapleural and pericardial pressures were measured via silastic cannulas. Pulmonary vein diameter was monitored by miniature mutual inductance coils. In the resting animal with sinus arrhythmia, inspiration increased heart rate and flow in the vena cava, and to a lesser extent, in the pulmonary vein. Left ventricular stroke volume (LVSV) varied directly with the right ventricular stroke volume (RVSV) in dogs with slow heart rates. Cardiac tamponade invariably caused tachycardia and a marked decrease in cardiac output, arterial pressure, pulse pressure, and stroke volume; venous pressure and diameter increased. Pericardial pressure, although markedly elevated, fell with inspiration paralleling the fall in intrapleural pressure. Flow in the pulmonary vein rose or remained constant with inspiration. Pulmonary vein diameter frequently increased with inspiration during tamponade, but only after the pulmonary artery diameter increased with the inspiratory surge. LVSV did not decline sharply with inspiration, and actually increased within 2 beats of the increase in RVSV. The sum of LVSV plus RVSV increased markedly with inspiration, contradicting the concept of fixed intrapericardial volume. Almost all of the changes of pulsus paradoxus reflect the normal respiratory effects on the RVSV, delayed by transit through the pulmonary bed and exaggerated by the small LVSV in a vasoconstricted state.
Enhancement of Coronary Vasodilator Action of Adenosine Triphosphate by Dipyridamole
Authors: AFONSO SKODA , O'BRIEN GEORGE S.
Published: June 2012

It has been reported that previously administered dipyridamole intensifies the coronary vasodilator action of adenosine compounds. In the present study, a combination of dipyridamole and ATP at doses that alone are ineffective was examined for its effect on the coronary sinus blood flow. In 10 anesthetized dogs, heart rate, arterial blood pressure, cardiac output, and coronary sinus blood flow were measured before and during a 20-min constant-rate infusion of (a) ATP alone, 1 mg/min; (b) a combination of ATP, 1 mg/min, and dipyridamole, 0.005 mg/kg/min; and (c) dipyridamole alone, 0.005 mg/kg/ min. Coronary sinus flow was measured by a newly developed thermodilution flowmeter. Consistently during the infusion of ATP or dipyridamole alone no changes in the measured parameters occurred, whereas during infusion of the combination a very marked and sustained elevation (+493%) of coronary flow occurred, associated with a moderate increase in cardiac rate (+37%) and output (+42%) and a decrease in arterial blood pressure (-17%). In 7 other dogs, coronary vasodilator responses to ATP were determined before and 1 hour after a single 10-mg dose of dipyridamole. After dipyridamole, the coronary vasodilator action of ATP increased 5- to 100-fold. In a third group of 3 dogs, dipyridamole did not enhance the coronary vasodilator effects of nitroglycerin, bradykinin, or acetylcholine.
Genetic Transmission of Congenital Membranous Ventricular Septal Defects in Selectively Inbred Substrains of Rats
Authors: FOX MARJORIE HOPKINS
Published: June 2012

Two inbred substrains of Long-Evans rats have been maintained under identical laboratory conditions. In one substrain (Olson-Goss) 25% of the neonates have spontaneously occurring membranous ventricular septal defects; in the other (California) only 4% are affected. Since a genetic etiology was indicated, two series of reciprocal crosses were made to evaluate the possibilities that the defects might result from an abnormal fetal genotype, a genetically abnormal intrauterine environment, or both. In both series parents of a highly defective litter ("high-incidence" pairs) were reciprocally mated to parents of a completely normal litter ("low-incidence" pairs). In Series I, all parental pairs were Olson-Goss animals; in Series II, the low-incidence pairs were California animals. Substitution of a low- for a high-incidence male consistently and appreciably decreased the incidence of defects in the progeny of high-incidence females. Conversely, low-incidence females produced a relatively large number of defective pups when mated to high-incidence males. These data suggest that the primary factor responsible for septal malformation is the fetal genotype rather than the intrauterine environment. Patroclinous reciprocal cross differentials, particularly marked in the substrain crosses, suggest, however, that secondary factors may also be implicated.
Glycogen Concentration in Working and Nonworking Ventricles of Isolated Dog Hearts
Authors: JEDEIKIN L. A. , BUCKLEY N. M.
Published: June 2012

Glycogen utilization in working and nonworking ventricles was studied at high (over 70 mg/100 ml) and low (27 to 61 mg/100 ml) arterial glucose concentrations and after insulin or epinephrine addition in 16 isolated ventricle preparations of dog hearts. Coronary perfusion and hemodynamic determinants of right ventricular work were controlled, and the left ventricle was kept unloaded. Time courses of change in ventricular glycogen concentration were determined during monitoring of heart rate, workload, arterial oxygen saturation, and coronary perfusion pressure. Epicardial samples for glycogen analysis were taken from each ventricle, and glucose uptake from circulating blood was determined. Glycogen loss was greater in working right than in nonworking left ventricles. In spontaneously fibrillating hearts, this difference was not observed, and there was greater glycogenolysis than during coordinated contraction. Insulin administration early in experiments led to equivalent glycogen loss in working right and nonworking left ventricles. There was glycogen preservation in both ventricles of fibrillating hearts. Epinephrine augmented glycogen loss in fibrillating hearts; depletion was never complete. Myocardial glucose uptake, corrected for red cell glycolysis, was proportional to initial arterial glucose concentration.
Influence of Potassium Depletion on Myocardial Concentration of Tritiated Digoxin
Authors: COHN KEITH E. , KLEIGER ROBERT E. , HARRISON DONALD C.
Published: June 2012

The influence of potassium deficiency on myocardial
3
H-digoxin concentration in the mouse was studied. Tritiated digoxin, 400 µg/kg, was injected intraperitoneally into mice, which were killed at varying time intervals, and the
3
H-digoxin was extracted. One-half of the mice were made potassium deficient by a diet free of potassium.

In control animals, myocardial
3
H-digoxin was maximal by 30 min and declined through 24 hours. There was no significant difference between the myocardial
3
H-digoxin of the control and potassium-depleted groups at ½ 1, 2, 6, or 16 hours, but at 24 hours a significantly higher concentration of digoxin was present in the potassium-deficient mouse hearts (23.6 ± 5.2 mµg/g) than in the control group (3.1 ± 1.5 mµg/g). Potassium-depleted mice with total renal failure, produced by bilateral ligation of the renal pedicle, showed increased myocardial
3
H-digoxin levels at 20 hours as compared with mice with renal failure but without potassium deficiency.

It is concluded that potassium deficiency may lead to increased concentrations of cardiac digoxin. The findings in the anuric animals suggest that diminished renal function produced by potassium depletion is not the sole mechanism of this retention of cardiac
3
H-digoxin.
Activity of the Vesicular Calcium Pump in the Spontaneously Failing Heart-Lung Preparation
Authors: GERTZ EDWARD W. , HESS MICHAEL L. , LAIN RICHARD F. , BRIGGS F. NORMAN
Published: June 2012

The in vitro calcium uptake activity has been examined in fragments of sarcoplasmic reticulum, i.e. vesicles, obtained from hearts spontaneously failing in the canine heart-lung preparation. The rate of uptake was found to be less than that observed for vesicles from control hearts. If the vesicles were prepared from a failed heart that had been treated in vivo with ouabain, then the rate of calcium uptake was normal. In vitro additions of ouabain increased the rate of calcium uptake only with vesicles prepared from failing hearts. This effect of ouabain on calcium uptake by vesicles appears, therefore, to be specific for the defect causing depression of calcium uptake. No evidence could be found that the depression of calcium uptake is due to uncoupling of the pump adenosine triphosphatase. Calcium uptake and adenosine triphosphatase activity were found to be proportionately depressed in the failing heart and proportionately restored by ouabain.
Responses of Individual Cardiac Chambers to Stimulation of the Cervical Vagosympathetic Trunk in Atropinized Dogs
Authors: RANDALL WALTER C. , PRIOLA DONALD V. , PACE J. B. , Randall David C. , Harold Spurgeon David C.
Published: June 2012

Employing multiple chamber pressure recording techniques, the presence of fibers within the right and left cervical vagosympathetic trunks which innervate both right and left ventricles has been demonstrated. Electrical excitation of the cervical vagosympathetic in the atropinized dog elicited a distinct increase in both rate of rise and in maximal systolic intraventricular pressures, with or without cardiac acceleration. It persisted during electrical pacing of the right ventricle. In many animals, the a-wave of the atrial pressure traces also showed augmentation, but this was not consistent or essential for the ventricular response. Although pulmonary vasoconstriction was not ruled out as a concurrent event, its contribution to right ventricular augmentation was not essential as demonstrated in bilateral, isovolumetric ventricular preparations. The evidence indicates the presence of adrenergic fibers in the cervical vagosympathetic trunk which are distributed to all four cardiac chambers. Their effects on the heart are abolished by the β-blocking agent, propranolol, and are unaffected by eserine administration.
Role of Acetylcholine in the Renal Vasoconstrictor Response to Sympathetic Nerve Stimulation in the Dog
Authors: MCGIFF JOHN C. , BURNS ROBERT B. P. , BLUMENTHAL MARVIN R.
Published: June 2012

The renal blood vessels were studied for a cholinergic determinant of their response to renal nerve stimulation. In dogs anesthetized with morphine and chloralose, control values were: mean aortic blood pressure 147 ± 4 mm Hg, renal blood flow 257 ± 12 ml/min. Acetylcholine (ACh) in 1-, 10- and 100-µg doses (all drugs given into the renal artery) increased renal blood flow, whereas 1000 µg of ACh reduced renal blood flow by 35%. After atropine and physostigmine, 1 µg of ACh did not alter renal blood flow, while 10, 100 and 1000 µg of ACh reduced renal blood flow by 6, 40 and 72%, respectively. After reserpine pretreatment, ACh in all doses increased renal blood flow (range of the means from 20 to 30%). The vasoconstrictor action of ACh was also blocked by phentolamine, guanethidine and hexamethonium. The renal vasoconstrictor response to renal nerve stimulation was blocked by guanethidine, but not by hexamethonium. These observations suggest that hexamethonium opposes ACh by barring its entry into the nerve terminals, whereas guanethidine blocks the intraneuronal release of norepinephrine by ACh. The vasoconstrictor response to nerve stimulation was reduced by atropine and augmented by physostigmine. Hemicholinium, which blocks the synthesis of ACh, attenuated the renal vasoconstriction produced by nerve stimulation. The results suggest that ACh may function in the canine kidney to liberate norepinephrine during activity of the sympathetic nerves.
Pulse Wave Velocity in the Main Pulmonary Artery of the Dog
Authors: BARGAINER JACK D.
Published: June 2012

Apparent phase velocities in the main pulmonary artery were calculated from simultaneous measurements of pressure at two sites in 11 anesthetized, open-chest dogs, at heart rates ranging from 24 to 240 beat/min. The distribution of apparent phase velocity with harmonic frequency was similar to that reported previously for input impedance and frequency. Phase velocity in the absence of reflections, estimated by averaging apparent phase velocities at frequencies from 9 to 23 cycle/sec, averaged 275 cm/sec in the control state and 417 cm/sec during the infusion of 5-hydroxytryptamine (serotonin). The elastic modulus of the pulmonary arterial wall implied by these velocities was calculated to be approximately 1.2 x 10
6
dyne/cm
2
in the controls and 2.7 x 10
6
dyne/cm
2
during serotonin. These results are consistent with previous observations on normal pulmonary vascular input impedance in the dog under these conditions, and with the relationships predicted by the Womersley equations, and suggest that the effects of serotonin on the input impedance spectrum are due in part to an increase in pulse wave velocity.
Anatomy of the Cardiac Conduction System in the Rabbit
Authors: JAMES THOMAS N.
Published: June 2012

Anatomy of the cardiac conduction system was studied in 15 rabbits with serial histologic sectioning of 4. The rabbit's sinus node is a simple and distinct structure located at the junction of the crista terminalis with the sinus intercavarum nearly midway between the two cavae; it contains an unusually large percentage of P cells but is not organized about a large central artery. The AV node and His bundle are relatively small and are displaced anteriorly by the large coronary sinus normally present in the rabbit because of its persisting left superior vena cava. The AV node is organized with input system and bypass tracts similar to those of man and the dog. Doth the AV node and His bundle contain many conspicuously large nerve trunks. The blood supply of the sinus node is from terminal small branches of both the right and left coronary arteries and that to the AV node and His bundle is from similar terminal branches of the septal artery only. The possible functional significance of some of these anatomic features is discussed.
Natriuretic Effect of Angiotensin in Dogs Revealed after Administration of Reserpine and Guanethidine
Authors: MCGIFF JOHN C.
Published: June 2012

In untreated dogs anesthetized with morphine-chloralose, a small dose of angiotensin (0.0375 µg/kg per min) produced a large reduction in renal blood flow, a smaller reduction in glomerular filtration rate and an antinatriuresis. A graded change in the excretion of sodium in response to angiotensin occurred after the successive administration of reserpine and guanethidine. In reserpinetreated dogs, angiotensin did not produce an antinatriuresis, whereas in the same dogs after giving guanethidine, a natriuresis occurred in response to angiotensin (from a control of 60 to 189 µEq Na/min). The effects of angiotensin on blood pressure and glomerular filtration rate were similar in all dogs. The renal vasoconstrictor effect of angiotensin was decreased in 3 of 8 dogs after guanethidine. At the high dose of angiotensin (0.375 µg/kg per min), the natriuresis was larger (from a control of 75 to 353 µEq Na/min) and was unrelated to changes in glomerular filtration rate or renal blood flow. In reserpine- and guanethidine-treated dogs, angiotensin increased sodium excretion sufficiently during renal arterial constriction to produce a large reduction in renal blood flow and the filtered load of sodium. These results suggest that angiotensin has a renal tubular action that is uncovered by sympathetic blockade produced by reserpine and guanethidine.
Myocardial Oxygen Consumption in Acute Experimental Cardiac Depression
Authors: GRAHAM THOMAS P. , ROSS JOHN , COVELL JAMES W. , SONNENBLICK EDMUND H. , CLANCY RICHARD L.
Published: June 2012

Myocardial oxygen consumption (MV
·
o
2
) during drug-induced cardiac depression was measured in 8 anesthetized, open chest dogs in which myocardial wall tension was controlled. The right side of the heart was bypassed and myocardial contractility was reduced with procaine HCl, propranolol, or pronethalol. MV
·
o
2
consistently fell during cardiac depression (avg = 1.52 ml/min per 100 g left ventricle or - 11.6%). These reductions occurred despite small increases in developed tension. Changes in the tension-time index, contractile element work, and contractile element power did not correlate invariably with ΔMV
·
o
2
, while reductions in velocity of the contractile elements at isotension, maximum left ventricular dp/dt, and the extent of shortening of the contractile elements and circumferential fibers were associated in every experiment with the reductions in MV
·
o
2
. The finding that negative inotropic influences are associated with a reduction in myocardial energy utilization, when considered with earlier observations showing that positive inotropic influences induce an augmentation of MV
·
o
2
, provides evidence that the inotropic state and its mechanical correlates are coupled with myocardial energy utilization by a mechanism that is independent of tension development.
Intracellular Po
2
and Its Regulation in Resting Skeletal Muscle of the Guinea Pig
Authors: WHALEN WILLIAM J. , NAIR PANKAJAM
Published: June 2012

Intracellular Po
2
in the gracilis muscle of lightly anesthetized guinea pigs was measured by means of an O
2
microelectrode to see (a) whether the Po
2
was low enough that it might limit O
2
consumption, and (b) whether it would increase with high O
2
breathing. The resting cell membrane potential was used to localize the electrode tip. Of 184 cells tested in 26 animals, 70 cells had a Po
2
of less than 1 mm Hg. Mean intracellular Po
2
was about 4 mm Hg. When 100% O
2
or 98% O
2
-2% CO
2
was administered while the electrode was in a cell, 60 of 89 cells tested (20 animals) showed no change in Po
2
. In the other 29 cells, the Po
2
increased by 5% or more. We have concluded that blood flow in resting skeletal muscle in the anesthetized guinea pig is regulated so as to maintain a low Po
2
-low enough that it could limit O
2
consumption.
Induction of Failure in Gas-Perfused Hearts by Intermittent Administration of Krebs Solution
Authors: GABEL LLOYD P. , BIHLER IVAN , DRESEL PETER E.
Published: June 2012

Our previous work has shown that kitten hearts perfused with a warm, moist mixture of 5% CO
2
-95% O
2
beat strongly for many hours. We now show that after 1 hr of gas perfusion, intermittent administration of small volumes of Krebs solution (5 ml every 30 min to total of 20 ml) causes progressive failure of the heart. Washout cardiac failure is accompanied by loss of protein from the hearts. We have isolated a cardiotonic material from the washout liquid by precipitation with ammonium sulfate. This material is more active in failed than in normal isolated kitten atria. Preperfusion with digitalis glycosides (10
-10
to 10
-9
g/ml) protects hearts against failure and loss of protein during periods of washout with saline.
Diffusion Processes Invalidating the Intra-arterial Krypton-85 Beta-Particle Clearance Method for Measurement of Skin Blood Flow in Man
Authors: SEJRSEN PER
Published: June 2012

Krypton-85 dissolved in 0.9% NaCl was injected into the femoral artery of man; β particles were measured over the skin of the crus. Cutaneous mean blood flow was calculated using the integral equation of Zierler based on the mean transit time analysis of clearance curves recorded from the cutaneous tissue; these calculations gave estimates which were only about one-fifth those obtained by other methods. The low estimates were caused by an intercom-partmental exchange of
85
krypton between the cutaneous and subcutaneous tissues, an exchange implying that both tissues influence the shape of the clearance curve recorded from the cutaneous tissue alone. This intercompart-mental exchange was effected not only by diffusion directly from the cutaneous to the subcutaneous tissue, but presumably also by transport from the blood streaming between the two tissues. The clearance rate of the tail of the curve was shown to correspond to that of the subcutaneous tissue. The errors distorting the clearance curve of β particles may invalidate the use of intra-arterial injection and measurement of clearance curves of β particles for measurement of blood flow in other tissues.
Effects of Propranolol and Its Stereoisomers upon Coronary Vascular Resistance
Authors: WHITSITT LEIGHTON S. , LUCCHESI BENEDICT R.
Published: June 2012

Responses of the coronary vascular bed to propranolol and its stereoisomers were studied in dogs anesthetized with allobarbital and urethane. The circumflex coronary artery was cannulated and perfused at a constant rate with blood from a femoral artery, coronary perfusion pressure being monitored as an index of coronary vascular resistance.
dl
-Propranolol (0.5 mg/kg iv) increased coronary vascular resistance and simultaneously reduced myocardial contractile force, heart rate, and systemic blood pressure. Approximately two thirds of the increase in coronary resistance was associated with the negative chronotropic action of propranolol. Intracoronary injections of
dl
-propranolol and
l
-propranolol increased coronary vascular resistance;
d
-propranolol increased resistance after an initial transient coronary dilatation. Intracoronary injections reduced contractile force in the pump-perfused area, but were without effects on heart rate and blood pressure. Reserpine pretreatment reduced, but did not abolish, the coronary vascular response to systemic propranolol; the chronotropic and inotropic responses were abolished. The responses to intracoronary
d
-propranolol were not altered. It was concluded that the increase in coronary vascular resistance following propranolol is due largely to the negative chronotropic effect of the drug and to an action of the drug which is unrelated to specific β-adrenergic receptor blockade.
Control of the Splanchnic Circulation in Man
Authors: PRICE HENRY L. , COOPERMAN LEE H. , WARDEN JOHN C.
Published: June 2012

Some effects of the β-adrenergic receptor blocker, propranolol, were studied in 20 normal, fasting, conscious men. The measurements made included cardiac output, splanchnic blood flow and oxygen consumption, arterial and hepatic venous blood pressure, and heart rate. The intravenous administration of propranolol (0.13 mg/kg) was followed by significant reductions in splanchnic blood flow and oxygen consumption, in cardiac output and in heart rate. Splanchnic perfusion pressure was unchanged; the splanchnic vascular resistance was significantly elevated. Previous treatment with glucose did not alter these findings. Phenoxybenzamine pretreatment lessened the increase in splanchnic vascular resistance which propranolol ordinarily caused. Ganglion-ic blockade with hexamethonium prevented all of the changes which propranolol produced in untreated individuals. These results may best be explained by assuming that the splanchnic circulation in man is influenced both by α receptors, which cause vasoconstriction when activated, and by β receptors, which when activated caused vasodilatation and increase oxygen consumption.
Work Performance of the Isolated Perfused Beating Heart in the Hereditary Myocardiopathy of the Syrian Hamster
Authors: BRINK ANDRIES J. , LOCHNER AMANDA , Kotzé J. C. N. , McGregor M.
Published: June 2012

The work performance of the isolated beating heart of control Syrian hamsters and hamsters suffering from an inbred myocardiopathy was studied in a system using a myographic differential force transducer. A stretch force of either 3.75 or 8.75 g was applied to the hearts. Myocardial metabolism of pyruvate-3-
14
C and palmitate-1-
14
C was studied with and without a stretch force. A definite reduction in work performance of the myopathic heart could be demonstrated. Peak height of contraction, tension-time index, tension time per minute and heart rate were significantly lower. The progressive myocardial fiber lengthening, caused by the stretch force, was less in the myopathic hearts.

No difference was observed between the uptake and oxidation of pyruvate-3-
14
C and palmitate-1-
14
C by control and myopathic hearts. The presence of a stretch force affected metabolism of both hearts in a similar manner. Two mechanisms for explaining the reduction in work performance by the myopathic heart were observed, namely, a reduction in heart rate and a relative inability of the myopathic muscle fibers to lengthen. The depressed mechanical performance could not be related directly with altered substrate metabolism or with reduction in total muscle mass.
An Electrophysiologic Correlate of Ouabain Inotropy in Canine Cardiac Muscle
Authors: EDMANDS ROBERT E. , GREENSPAN KALMAN , FISCH CHARLES
Published: June 2012

Action potentials were recorded via intracellular microelectrodes, together with recordings of isometric-contractile tension, from isolated trabecular muscles of canine ventricle. The effects of administration of ouabain solution in concentrations varying from 1.7 x 10
-7
to 5 x 10
-4
M were recorded. The early inotropic effects of ouabain (increase in contractile force) were accompanied by changes in configuration of the action potential identical to those associated with interval-dependent potentiation in the control state, that is, abbreviation of phase 2 and lengthening of phase 3, without significant change in duration of the action potential. The progressive administration of ouabain, while associated with contractile enhancement of the regularly stimulated contraction was also accompanied by a loss of the contractile increment associated with poststimulation potentiation; this loss of interval-dependent potentiation corresponds to a loss of interval-dependent alteration of the action potential. Thus, both interval-dependent contractile potentiation and ouabain inotropy correlate consistently with phase 2 abbreviation of the accompanying action potentials.
Factors Determining Vulnerability to Ventricular Fibrillation Induced by 60-CPS Alternating Current
Authors: SUGIMOTO TSUNEAKI , SCHAAL STEPHEN F. , WALLACE ANDREW G.
Published: June 2012

Very weak, 60-cps alternating current applied directly to the heart can cause ventricular fibrillation; greater current strength is required to induce ventricular fibrillation with a single shock delivered during the vulnerable period of the cardiac cycle. The present experiments were designed to examine the basis of this difference. The studies were performed in anesthetized open-chest dogs. The current strength required to induce ventricular fibrillation was 0.52± 0.16 ma with 60 cps for 5 sec, and 15.0±4.3 ma with a single square-wave pulse of 10 msec. However, when the duration of 60 cps was reduced to produced only 4, 3, 2, or1 ventricular response, the threshold for ventricular fibrillation after the last response was 0.4, 2, 18, or 24 ma respectively. After any given number of successive premature ventricular responses, the fibrillation threshold was comparable with either 60 cps or a single pulse. We concluded that, if an accelerating ventricular tachycardia that is produced by 60-cps stimulation is of sufficient duration (5 or 6 beats), the VF threshold is reduced progressively after each premature ventricular response, thus making it possible to include VF with very weak current.
Nucleic Acid Synthesis in Enlarged Hearts of Rats with Nutritional Anemia
Authors: KORECKY BORIVOJ , FRENCH IAN W. , Layberry R. A. , McKerral A. M.
Published: June 2012

Cardiac enlargement was produced in three groups of male rats by maintaining them on a diet low in iron. Hearts from anemic rats increased approximately 100% in weight compared to hearts from normal rats. When compared to control cardiac tissue, no consistent significant changes in the
concentration
of DNA, RNA, or protein occurred in any of the groups. The
total
amount of all three constituents increased significantly in the enlarged hearts; this increase was proportional to the degree of cardiac enlargement. The data indicate that nuclear and cytoplasmic material increased equally in cardiac enlargement due to nutritional anemia. This and other observations in the literature suggest hyperplasia as the most likely explanation.
Monitoring Cerebral Blood Flow and Oxygen, Glucose, Lactate and Ammonia Metabolism
Authors: MEYER JOHN S. , GOTOH F. , AKIYAMA M. , YOSHITOKE S.
Published: June 2012

New application of methods for monitoring cerebral blood flow and cerebral arteriovenous oxygen, glucose, lactate and ammonia differences are described. Results of trials of their validity in monkeys during experimental procedures are described. The apparatus includes infrared gas analyzers for monitoring arteriovenous differences after diffusion of nitrous oxide through silastic, electromagnetic flowmeters for monitoring cerebral venous outflow, the Technicon apparatus for measuring arteriovenous differences for lactate, glucose and ammonia, and the Guyton analyzer for monitoring cerebral arteriovenous oxygen differences. Cerebral blood flow in the monkey measured by the nitrous oxide method was 61 ml/100 g brain per min, cerebral oxygen consumption was 2.8 to 3.35 ml/100 g brain per min, cerebral glucose consumption was 3.52 mg/100 g brain per min, cerebral arteriovenous lactate difference was 1.1 mg/100 ml, cerebral arteriovenous ammonia difference was 2 mg/100 ml. Inhalation of 100% oxygen, 5% CO
2
in air, 20% CO
2
in air and hyperventilation caused no change in cerebral oxygen, glucose, lactate, and ammonia metabolism. During anoxic anoxia, cerebral glucose consumption increased and cerebral oxygen consumption decreased significantly. During seizures, cerebral metabolic rate for oxygen increased. No important changes in ammonia metabolism were noted. It was concluded that it is feasible to apply these methods concurrently in patients with cerebrovascular disease before and after therapeutic trials.
Contraction Dependency of the Positive Inotropic Action of Cardiac Glycosides
Authors: MORAN NEIL C.
Published: June 2012

The concept that the positive inotropic effect of cardiac glycosides is dependent on the contractile state of the myocardium was tested. Isolated left atria of rabbits, when driven electrically at 15, 30, 60 and 120/min (at 30, 33, or 37°C), responded to ouabain (I µ/ml) in proportion to the number of contractions and not to the time of exposure or frequency of drive. Contraction-related effects were proportional to concentration of ouabain, acetylstrophanthidin, and digoxin. A contraction-related effect of ouabain was observed in anesthetized dogs with surgical A-V block, ventricular electrical drive and right ventricular contractile force recording. Quiescent rabbit atria exposed to ouabain for 30 min at 30°C and then washed in ouabain-free medium, showed minimal positive inotropic effect when stimulation was resumed. Toxic concentration of ouabain (5 µg/ml) in contact with quiescent atria for 30 min and then washed out, on resumption of stimulation had an immediate positive intropic (but no toxic) effect which diminished progressively, in contrast to the rapid development of toxic effects (ectopic contractions and contracture) in atria exposed to this dose of auabain during repetitive contractions. It is concluded that a major part of the positive intropic effect of cardiac glycosides is contraction dependent.
Effect of Exteriorization of the Sheep Fetus on Its Cardiovascular Function
Authors: HEYMANN MICHAEL A. , RUDOLPH ABRAHAM M.
Published: June 2012

Exteriorized sheep or goat fetuses, with placental circulation continuing, have been extensively used for measurements of fetal cardiovascular function. However, the effects of this procedure on fetal cardiovascular function have not been assessed. We inserted vinyl catheters into an umbilical vein, an umbilical or fetal hindlimb artery, and a hindlimb vein. We measured umbilical arterial and venous blood gas tensions, umbilical blood flow using the steadystate diffusion antipyrine method, and fetal arterial and umbilical venous pressures before and after delivery by cesarean section. Following exteriorization, placental vascular resistance consistently increased and umbilical blood flow decreased. Umbilical venous Po
2
increased, but umbilical arterial and venous pH and Pco
2
and arterial Po
2
did not change significantly. Thus exteriorization of the fetus produces major changes in the fetal circulation, but these changes are not indicated by any major alterations in fetal blood gases and pH.
Pulmonary Vasoconstriction Elicited by Stimulation of the Hypothalamic Integrative Area for the Defense Reaction
Authors: ANDERSON FRED L. , BROWN ARTHUR M. , Concilia Pasquale A.
Published: June 2012

Changes in the pulmonary circulation evoked by stimulation of the hypothalamic integrative area for the defense reaction were studied in 22 cats anesthetized with a chloralose-urethane mixture. Pulmonary arterial pressure and flow, left and right atrial pressures, aortic pressure, arterial flow to the skinned hind limb, and heart rate were all significantly increased. The calculated pulmonary vascular resistance was also significantly increased. The rise in pulmonary vascular resistance was abolished by bilateral stellectomy or by hexamethonium infusion; it was not affected by bilateral cervical vagotomy. Therefore, the increase in pulmonary vascular resistance was mediated by the thoracic sympathetic nerves. The increase in pulmonary arterial flow was mainly caused by an increase in heart rate; a small rise in calculated stroke volume also occurred.
Sodium and Potassium Sensitivity of Calcium Uptake and Calcium Binding by Dog Cardiac Microsomes
Authors: KATZ ARNOLD M. , REPKE DORIS I.
Published: June 2012

Concentrations of KCl and NaCl below 1.0 M increased Ca uptake (in the presence of oxalate) by dog cardiac microsomes purified on sucrose density gradients; higher concentrations of these salts decreased Ca uptake. At lower microsome concentrations, where calcium uptake was maximal, replacement of KCl by equimolar amounts of NaCl decreased both the rate and extent of Ca uptake. The uptake of Ca in mixtures of NaCl and KCl was that expected from the presence of each cation alone, and bore no obvious relationship to the (Na
+
+ K
+
)-activated ATPase associated with sodium transport. Ca binding (in the absence of oxalate) was increased by concentrations of NaCl and KCl up to approximately 0.12 M when the reaction mixture contained 5 mM ATP; higher concentrations of the alkali-metal salts reduced Ca binding. A similar dual action of Na
+
and K
+
on Ca binding was seen in the absence of ATP, but Ca binding was maximal at approximately 0.01 M KCl. The reduced Ca binding at high concentrations of KCl in the presence of ATP showed some characteristics suggesting competition between K
+
and Ca
2+
for a single binding site, but double reciprocal plots of the data did not meet the strict criteria for a classical competitive reaction. Thus, while these microsomal membranes show some of the properties of an ion exchanger, these interactions are more complex, in that, at low ionic strengths, Ca binding is facilitated by addition of alkali-metal salts. Ca binding was not altered by replacing K
+
with Na
+
, and specific competition between Na
+
and Ca
2+
was not seen in deoxycholate-treated or sonicated microsomes. Thus, the site for the proposed Na
+
-Ca
2+
competition that controls myocardial contractility has not been found.
Effect of High Molecular Weight Dextran on Experimental Hypercholesterolemia
Authors: BRAHMANKAR DAMODAR M. , CONNOR WILLIAM E.
Published: June 2012

Thirty ml of 6% dextran (mol wt 70,000) was given intravenously daily to rabbits that were hypercholesterolemic from the ingestion of a 0.5%-cholesterol diet. Serum cholesterol concentrations were reduced from 990 ± 103 mg/100 ml to 676±79 mg/100 ml after 3 days and to 331±35 mg/100 ml after 7 days of dextran treatment. With the cessation of dextran infusions, serum cholesterol levels rose promptly above the pretreatment levels reaching 1346±156 mg/100 ml by the seventh day after treatment. Similar changes occurred in serum phospholipid and triglyceride values. The chief reason for the reduction of serum lipids was the expansion of plasma volume as a result of the dextran treatment. Other factors had a less significant role. Dextran did not change the cholesterol content of most tissues including aortic cholesterol. Liver cholesterol content actually increased. The effects of dextran were only temporary and were not accompanied by cholesterol mobilization from the tissues.
Effects of Cell Density and Low K on Action Potentials of Cultured Chick Heart Cells
Authors: LIEBERMAN MELVYN
Published: June 2012

Hearts from 7-day-old chick embryos were separated by 0.05% trypsin and subsequently cultured in a medium containing low (1.4 mM) and normal (4.4 to 5.6 mM) potassium (K) concentration. A method was developed for controlling environmental conditions (pH, temperature, osmolarity) of 1- to 3-day. old cultured heart cells during intracellular recording with microelectrodes. No apparent differences were noted in the measurement of the several components of the action potential as a function of incubation time. Action potential configurations recorded from cells in dense areas of a culture were noticeably different from those potentials obtained in sparse areas of the same culture; the latter were similar to those of the slowly conducting cardiac junctional tissues. This difference was observed both in the presence of normal and low K. The transmembrane potential recorded from cells in densely populated areas in the normal K medium was characterized by large amplitude and steady, high resting potential whereas that recorded from cells in similar areas in the low K medium had a small amplitude, low resting potential and prominent diastolic depolarization. The tissue cultured in low K also showed a tendency to fibrillate and spontaneously defibrillate.
Regulation of Pulmonary Capillary Blood Volume by Pulmonary Arterial and Left Atrial Pressures
Authors: KARP ROBERT B. , GRAF PAUL D. , NADEL JAY A.
Published: June 2012

We used single-breath CO diffusing capacity to study the effect of changes in pulmonary arterial and left atrial pressures on pulmonary capillary blood volume in 15 supine dogs whose lungs were perfused with a nonpulsatile pump. Effect of pulmonary arterial pressure: When left atrial pressure measured relative to the bottom of the lungs ≤ alveolar pressure, increasing pulmonary arterial pressure increased diffusing capacity markedly (mean, 0.71 ml/min x mm Hg per mm Hg change in pulmonary arterial pressure). When left atrial pressure ≥ alveolar pressure plus the height of the lungs, increasing pulmonary arterial pressure had less effect on diffusing capacity, although blood flow was increased through a wide range (mean, 0.22 ml/min x mm Hg CO per mm Hg increase in pulmonary arterial pressure). Effect of left atrial pressure: At zero flow, increasing left atrial pressure increased diffusing capacity markedly; when pulmonary arterial pressure was high, increasing left atrial pressure had no significant effect on diffusing capacity. Increasing bronchial arterial pressure from 0 to 150 mm Hg or inhaling 10.5% CO
2
had no effect on diffusing capacity. Injection into the pulmonary artery of glass microspheres decreased diffusing capacity only when left atrial pressure was low; their effect was exaggerated when pulmonary arterial pressure was high in the control state.
Use of a Local Indicator Dilution Technique for the Measurement of Oscillatory Flow
Authors: LOWE R. D.
Published: June 2012

An indicator dilution method for measuring oscillatory flow in a vessel is analyzed in terms of a mixing chamber with a constant volume. For the correct measurement of mean flow, the time constant of detection of the indicator should be very much shorter than the shortest time constant of the mixing volume. The performance of such a system was examined with a thermal indicator. Although the apparent mixing volume was found not to be constant but to vary with flow, the method showed no significant error in the measurement of mean flow. There was no significant "distance distortion error" when the indicator was detected at two different points downstream from the site of infusion; this was attributed to the pattern of mixing, with detection within or close to the limits of the mixing volume. It is concluded that a properly designed indicator dilution system can measure mean blood flow without significant error, even when there is an socillatory component.