bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Acute Asphyxia and Deep Hypothermia on the State of Binding of Lysosomal Acid Hydrolases in Canine Cardiac Muscle
Authors: LEIGHTY EDITH G. , STONER CLINTON D. , RESSALLAT MEHDI M. , PASSANANTI G. THOMAS , SIRAK HOWARD D.
Published: June 2012

The amount and state of binding of three lysosomal acid hydrolases, acid phosphatase, cathepsin, and β-glucuronidase, were studied in canine cardiac muscle following severe asphyxia and deep hypothermia. The studies were done on adult mongrel dogs anesthetized with sodium pentobarbital. Asphyxia was produced by tracheal occlusion, and was maintained until the onset of cardiac arrest (6 to 10 min). Hypothermic conditions were achieved by placing the heart on partial bypass through a heat exchanger. The heart was cooled to 6 to 10°C and held at this temperature for 30 min while circulation and respiration were maintained by artificial means. Control dogs were subjected to similar surgical procedures. Immediately following the experiments, the whole hearts were removed, cooled to 0 to 4°C, homogenized, and fractionated into supernatant and lysosomal fractions. The levels of bound and free acid hydrolases were estimated in the whole homogenates and fractions. Asphyxia produced a large shift of acid hydrolase activity from a bound form to a free form, as evidenced by elevated ratios of free to bound activity in the whole homogenates and elevated ratios of supernatant to lysosomal activity with respect to the fractions. Hypothermia did not alter the binding status of the lysosomal enzymes. These findings suggest that lysosomal enzymes play a major role in asphyxic damage to the heart.
Physiological Differences between the Effects of Neuronally Released and Bloodborne Norepinephrine on Beta Adrenergic Receptors in the Arterial Bed of the Dog
Authors: GLICK GERALD , EPSTEIN STEPHEN E. , WECHSLER ANDREW S. , BRAUNWALD EUGENE , Lewis Robert M. , McGill Richard D.
Published: June 2012

This investigation was designed to define the role of the beta adrenergic receptors in the regulation of peripheral vascular resistance and to determine whether norepinephrine released from nerve terminals acts at the same receptor sites in the arterial bed as injected norepinephrine. In 34 anesthetized dogs the skinned hindlimb was perfused at a constant flow rate, and in 8 dogs a segment of the splanchnic vascular bed was similarly perfused through the aorta. The hemodynamic responses of the isolated perfused beds of control dogs were compared with those of dogs in which the alpha receptors had previously been blocked with phenoxybenzamine, thereby maximizing any contribution of the beta receptors. In the control animals, both carotid sinus hypotension and norepinephrine administered directly into the perfused segment increased vascular resistance. In those animals subjected to alpha-receptor blockade, carotid sinus hypotension still caused reflex vasoconstriction, though it was considerably attenuated, but intra-arterially injected norepinephrine produced vasodilation. Following subsequent beta-receptor blockade, no potentiation of reflex constriction occurred, although the response to injected norepinephrine reverted to constriction. These findings suggest that norepinephrine released from nerve terminals in the arterial tree does not produce physiologically significant beta-receptor stimulation; humorally transported norepinephrine, however, stimulates both alpha and beta receptors.
Vasomotor Responses in the Hindlimb of Newborn Calves
Authors: MILLIGAN JOHN E. , ROACH MARGOT R. , TALNER NORMAN S.
Published: June 2012

The reflex control of the hindlimb circulation was examined in 9 newborn calves under chloralose anesthesia by measuring iliac arterial pressure-flow curves. Asphyxia always caused vasoconstriction which was abolished or greatly reduced by sciatic nerve section. Vasomotor tone was present a few hours from birth, as shown by an increase in flow on sciatic nerve section and by drug action. It is concluded that autonomic control of the systemic circulation is effective in this species at birth.
The Ultrastructure of the Heart in Systole and Diastole
Authors: SONNENBLICK EDMUND H. , ROSS JOHN , COVELL JAMES W. , SPOTNITZ HENRY M. , SPIRO DAVID
Published: June 2012

The relations between ultrastructure and function have been examined in the canine left ventricle under known hemodynamic conditions. Left ventricles of normal dogs were fixed acutely by rapid perfusions of the coronary arteries in either diastole or systole, and also following acute ventricular distension, or potentiation of contraction. Sarcomere lengths at the midwall of the left ventricle averaged 2.07 µ at end diastole and 1.81 µ at end systole, changes that are adequate to explain the degree of normal ventricular emptying. Following marked ventricular emptying induced by postextrasystolic potentiation, sarcomeres shortened to an average of 1.60 µ; with acute ventricular distension resulting from over-transfusion, average sarcomere length in diastole increased to 2.25 µ. In each instance, sarcomere lengths correlated with the changes in sarcomere length predicted from changes in the dimensions of a thick-walled sphere. The importance of dispersion of sarcomere length within a given layer of the ventricular wall was noted and its potential significance discussed.
Effects of Ouabain on Force of Contraction, Oxygen Consumption, and Metabolism of Free Fatty Acids in the Perfused Rabbit Heart
Authors: GOUSIOS ARISTIDES G. , FELTS JAMES M. , HAVEL RICHARD J.
Published: June 2012

Isolated rabbit hearts were perfused with a suspension of red cells which assured adequate oxygenation. Ouabain added to the perfusate (2.8 x 10
-7
M final concentration) promptly increased the force of contraction and oxygen consumption of the hearts. These events appeared to occur simultaneously. The extraction ratio of palmitate-1-
14
C added to the perfusate (0.31) was not altered by ouabain. However, ouabain increased the oxidation of the extracted palmitate from an average of 34% to an average of 71% at the time intervals studied.
Role of Acetylstrophanthidin in Augmenting Myocardial Oxygen Consumption
Authors: COLEMAN HENRY NEAL
Published: June 2012

A polarographic method was used to determine the effects of acetylstrophanthidin on myocardial oxygen consumption (MV
·
O
2
) of 19 cat papillary muscles contracting under both afterloaded and isometric conditions. Under afterloaded conditions, acetylstrophanthidin shifted the force-velocity relation to the right and produced increments in both the extent and velocity of shortening at constant levels of developed force. These changes in myocardial mechanical behavior after strophanthidin were always associated with an increased MV
·
O
2
. Since both the extent and velocity of shortening increased following augmentation of the contractile state with glycoside, consideration of the individual effect of these variables in myocardial mechanical behavior on MV
·
O
2
was precluded. Therefore, experiments were performed on isometrically contracting muscle to evaluate the effect of changes in the velocity of contraction on MV
·
O
2
independent of changes in contractile element shortening. Comparison of the MV
·
O
2
of isometric contractions at equal levels of developed tension (and thus equivalent amounts of internal contractile element shortening) was accomplished by decreasing initial muscle length after augmentation of the contractile state by acetylstrophanthidin. Under these conditions, augmentation of the contractile state, characterized by an increase in the velocity of contraction, was associated with an increased MV
·
O
2
. Thus it is concluded that the effect of acetylstrophanthidin is to increase MV
·
O
2
at a constant load and that this augmentation of MV
·
O
2
can be related to the change in contractile state of the muscle.
A Method for Studying Isolated Resistance Vessels from Rabbit Mesentery and Brain and Their Responses to Drugs
Authors: UCHIDA EIICHI , BOHR DAVID F. , HOOBLER SIBLEY W.
Published: June 2012

A technique has been developed for studying the reactivity of single, isolated resistance vessels, 50 to 250 µ o.d., perfused at constant flow rate. The validity of the method is established because responses to a given stimulating agent are reproducible and stable over a reasonable period of time. The magnitude of the response is dependent on the perfusion pressure, being maximal at a physiological pressure level. Resistance vessels from mesentery and brain of normal rabbits were compared with respect to their threshold for response to several vasoconstrictors. The results reaffirmed the individuality of smooth muscle from different vascular beds. Cerebral and mesenteric vessels are alike in the dose required for threshold constrictor response to KCl, angiotensin and plasma, but differ in that cerebral vessels have a higher threshold for response to epinephrine, norepinephrine and serotonin, and a lower threshold for response to vasopressin, than mesenteric vessels. Since the differences in threshold between vessels from the two sources are not the same for all stimulating agents, it seems probable that smooth muscle of the cerebral vessels is not generally less sensitive to all stimuli than that of mesenteric vessels, but that vessels from the two sources differ in the "number of receptors" for the several vasoactive agents.
Incorporation of
14
C-Labeled Acetate into Lipid by Isolated Foam Cells and by Atherosclerotic Arterial Intima
Authors: DAY ALLAN J. , WILKINSON GWENDOLINE K.
Published: June 2012

The synthesis of lipid by rabbit atherosclerotic intima incubated in vitro has been investigated and compared with that of foam cells isolated from intimal lesions. In the atherosclerotic arterial intima,
14
C-labeled acetate is readily incorporated into the lipid fraction, most of the label being found in the phos-pholipid and cholesterol ester fatty acid fractions. Minimal incorporation into triglyceride, fatty acid, and cholesterol occurred. The major phospholipid synthesized was lecithin but significant incorporation into phosphatidyl inositol, phosphatidyl ethanolamine, and sphingomyelin also took place. The fatty acids synthesized were predominantly saturated in the phospholipid fraction. More monounsaturated fatty acids were present in the cholesterol ester fatty acids, but in both moieties little polyunsaturated fatty acids were labeled by the acetate. Isolated foam cells were also shown to incorporate
14
C-labeled acetate into both phospholipid and cholesterol ester fatty acids. The foam cells, however, incorporated a significantly higher proportion of acetate into cholesterol ester than did the whole intima. The fatty acids synthesized by the foam cells were more polyunsaturated in both the phospholipid and the cholesterol ester fraction than was the case with the whole intima. The relevance of these findings to the origin of lipid in the atherosclerotic lesion is discussed.
Myocardial Cell and Sarcomere Lengths in the Normal Dog Heart
Authors: LAKS MICHAEL M. , NISENSON MICHAEL J. , SWAN H. J. C.
Published: June 2012

The purpose of this study was to measure myocardial cell and sarcomere lengths at the bases and apices of the right (RV) and left ventricle (LV) of 4 normal canine hearts. The RV and LV were simultaneously fixed with glutaraldehyde at zero transmural pressure. Sections of trabeculae carneae were taken from the 1 cm cut at the bases (free wall) of the RV and LV. They were further fixed with osmium tetroxide, embedded in Epon 812, sectioned at ½ to 1 µ and stained with azure II and methylene blue. Measured from photomicrographs (X 1,000) taken with the phase microscope, mean cell length was 70.9 µ±1.49 (SEM); no statistical difference existed between the cell lengths at the bases and apices of the RV and LV. From adjacent tissue, the measurements of sarcomere lengths made from photomicrographs (phase microscope, oil immersion lens, enlarged to X 4,000) were not statistically different from those made with the electron microscope (P>0.9). The sarcomere lengths at the LV base were the shortest-2.16 µ±0.002 (SEM), followed by the LV apex, 2.28 µ±0.005 (SEM); RV base, 2.41 µ±0.006 (SEM); and RV apex, 2.46 µ±0.003 (SEM). These variations in sarcomere length show the importance of specifying the site of sampling of myocardial tissue. The sarcomere lengths were related inversely to the thickness of the ventricular wall. This observation may be considered the structural reflection of the lesser distensibility of the left base as compared with the right apex, and may be simply the manifestation of the fact that the left base contains more muscle fibers.
Interactions between Changes in the Intensity and Duration of the Active State in the Characterization of Inotropic Stimuli on Heart Muscle
Authors: BUCCINO ROBERT A. , SONNENBLICK EDMUND H. , SPANN JAMES F. , FRIEDMAN WILLIAM F. , BRAUNWALD EUGENE
Published: June 2012

The responses of isolated cat papillary muscles and left atrial strips to a variety of procedures were classified systematically according to the induced changes in peak tension (T), mean rate of tension development (δT/δt), and time to peak tension (TTP). Increasing temperature from 25° to 37°C augmented δT/δt but reduced TTP reciprocally so that T remained constant. Increased frequency of contraction, thyroid hormone, and increased temperature markedly augmented δT/δt but shortened TTP, with relatively little alteration in T. Norepinephrine, tyramine, paired electrical stimulation, strophanthidin, and calcium increased T by augmenting ΔT/δt proportionately more than they reduced TTP. Acetylcholine and serotonin augmented T by raising δT/δt with relatively little effect on TTP. Strontium increased T by causing both a prolongation of TTP and an augmentation of δT/Δt. Depression of T in muscles from failing hearts occurred primarily by a reduction of δT/δt, and the negative inotropic effects of hypoxia or pentobarbital resulted from reductions in both δT/δt and TTP. In muscles from hypothyroid cats, depression of δT/δt was partially compensated for by prolongation of TTP. Since δT/δt is related to the intensity of the active state and TTP to its duration, such analysis of these variables should provide a framework for the characterization and quantitative comparison of various types of inotropic stimuli.
An Electromagnetic Catheter-Flowmeter
Authors: KOLIN ALEXANDER , ARCHER JAMES D. , ROSS GORDON
Published: June 2012

An electromagnetic flowmeter incorporated into a catheter is described. The catheter is introduced into the aorta via the femoral artery. The flow sensor is located some distance below the catheter tip and is sensitive to flow at right angles to the catheter. A crater-like elevation at one end of the transducer lumen permits funnel-like connection of the transducer to the ostium of an aortic branch. The transducer thus measures the blood flow through a selected branch of the aorta. It is pressed against the branch artery by arching the catheter by means of a pull-wire. A reliable and readily reproducible zero-flow baseline is obtained by slightly withdrawing the lumen of the transducer from the branch ostium, thus closing the lumen by the aortic wall. Records of phasic blood flow in the left renal and superior mesenteric arteries of a dog are presented. The calibration was accomplished by comparison with a calibrated noncannulating electromagnetic flow transducer. Reliable calibration can also be performed in vitro.
Study of Erythrocyte Aggregation by Blood Viscometry at Low Shear Rates Using a Balance Method
Authors: BENIS A. M. , LACOSTE J.
Published: June 2012

Abalance method was used to investigate the viscometric behavior and aggregation properties of blood at very low shear rates. The system was essentially a parallel-plate viscometer, consisting of a thin brass plate suspended by a fine wire from one end of an analytical beam balance. The yield shear stress of a sample was obtained directly by recording stress relaxation curves. Results were obtained for homogeneous Newtonian and non-Newtonian fluids and for blood and various red cell suspensions. It was found that human and canine blood behave as fluids exhibiting a yield stress. Suspensions of red cells in saline had much smaller values of yield stress, which is consistent with greatly diminished erythrocyte aggregation when fibrinogen is lacking. Measured values of the yield stress were in the range of 0.001 to 0.1 dynes/cm
2
.
Blood Flow through Terminal Arterial Vessels after Denervation of the Bat Wing
Authors: WIEDEMAN MARY P.
Published: June 2012

Previous studies of microcirculation in the denervated wing of the unanesthetized bat showed that major arterial vessels increased markedly in diameter and lost their ability to contract spontaneously. Arteriolar vessels did not show such an increase in diameter, and furthermore their spontaneous contractile activity increased. These observations led to the idea that regulation of blood flow and blood pressure might be continued to some degree in the absence of central nervous control through enhanced activity of arteriolar vessels which just precede the capillary nets.

Therefore a thorough study by direct microscopic observation of the behavior of arterial vessels in the following surgical and pharmacological denervation was made. The data support the hypothesis that loss of tone and loss of contractile activity in the large arterial vessels following denervation produce an increase of tone and activity in the smaller, more distally located vessels, thereby causing a redistribution of the site of regulation of flow through capillary nets. The largest arterial vessels showed and increase in average diameter of 38% after surgical denervation, while the terminal arterioles showed a decrease in average diameter of 24%. Neither phenoxybenzamine (Dibenzyline) norpentolinium (Ansolysen) were as effective as surgical denervation in producing relaxation of the large arterial vessels. Neither drug inhibited spontaneous contractile activity of the terminal vessels.
Dissociation of Circulating Renin and Erythropoietin in Rats
Authors: DONATI R. M. , BOURGOIGNIE J. J. , KUHN C. , GALLAGHER N. I. , PERRY H. M. , Kurz Linda
Published: June 2012

Renin and erythropoietin activities were measured in the plasma of 110 rats exposed to various conditions designed to dissociate the two renal "hormones." In acute experiments, intraperitoneal injection of polythiazide increased renin activity but did not change erythropoietin activity; exposure to low oxygen tension increased erythropoietin activity and caused an insignificant decrease in renin activity. In chronic experiments, salt restriction or the combination of salt loading and desoxycorticosterone for 2 weeks increased or decreased renin activity, respectively, without changing erythropoietin activity. The combination of chronic salt loading and acute hypoxia reduced renin activity and increased erythropoietin activity. In the final experiment, intraperitoneally injected cobaltous chloride acutely increased erythropoietin activity without markedly altering renin activity. Without contributing to the solution of the problem of the cell origin of erythropoietin, the present study clearly indicates that the secretion of renin and erythropoietin can be dissociated.
Abnormal Response of the Pulmonary Artery of the Rabbit after High Frequency Sympathetic Nerve Stimulation
Authors: BEVAN JOHN A. , NEDERGAARD OVE A.
Published: June 2012

When the sympathetic nerve supply (right recurrent cardiac nerve) to a ring of the pulmonary artery of the rabbit is stimulated repetitively in vitro at frequencies of 10/second or more, the following changes occur which are not seen after stimulation at lower frequencies. (1) The minimum number of pulses in a train needed to cause a just-detectable contractile response is reduced from a mean of 7 to unity; the higher the frequency of repetitive stimulation the fewer the number of repetitive pulses needed to effect this change. (2) The basal tone of the blood vessel exhibits fairly rapid, small, spontaneous fluctuations. (3) The resting or basal tone of the vessel slowly increases for 1/2 to 2 hours. It is speculated that changes 1 and 2 may be the result of an irreversible change in transmitter storage or release mechanisms.
Supernormality in Bachmann's Bundle
Authors: CHILDERS R. W. , MERIDETH J. , MOE G. K.
Published: June 2012

A supernormal phase of conduction between right and left atria was observed in the exposed hearts of anesthetized dogs. Interatrial conduction time of premature atrial responses was reduced by as much as 17% during the early phase of diastole, relative to the conduction interval of basic driven responses. The supernormal phase lasted from 60 to 140 msec and was greater at slower basic driving frequencies. A brief phase of supernormal excitability was also found in the specialized cells of Bachmann's bundle from puppy hearts in vitro. Supernormal conduction was not observed within the atrial appendages (i.e., in areas not supplied by specialized conducting bands); supernormal excitability was not demonstrable in cells of ordinary atrial myocardium. Although vagal stimulation abbreviated transatrial conduction time, atropine did not abolish the phase of supernormality.
Correlation of Visco-Elastic Properties of Large Arteries with Microscopic Structure
Authors: APTER JULIA T. , MARQUEZ ELSA
Published: June 2012

Nine aortas from recently killed dogs were sectioned into 21 or more ring segments supported horizontally on two hooks in Ringer's solution. One hook oscillated sinusoidally from .01 to 21 Hz to stretch the segments 1.2% in excess of 4 or more mean strain levels from 5 to 100%. The segments were kept at 4 temperature levels (0°, 20°, 37°, 60°C). The other hook was coupled to a force transducer. At frequencies below 1 Hz, the force registered was sinusoidal with the same frequency as the stretch which it led, unless the specimen contained demonstrably contracted smooth muscle; then the stress was nonlinear and lagged behind the strain at frequencies below .05 Hz. As frequencies rose above 1 Hz, the force amplitude rose to a maximum, resonating at frequency ω
r
, which was higher at higher initial strains. Concurrently the phase shift increased to 90° at another frequency ω
90
. When ω
90
= ω
r
, viscous losses were negligible, a fact confirmed by other data in this and other studies and generally implicating collagen. When ω
90
> ω
r
, viscous losses were appreciable, in agreement with other measurements and implicating either muscle or elastin. These two wall components could be distinguished from each other by responses to drugs and to changes in temperature. Absolute dynamic modulus, storage modulus, loss modulus, phase shift, and loss angle measured from stress-strain loops compared favorably with similar measurements published for other visco-elastic materials and with viscous and elastic constants obtained from stress-relaxation experiments on aorta.
Studies of Cat Heart Muscle during Recovery after Prolonged Hypothermia
Authors: TAMAI TADASI , KAGIYAMA SHUNSUKE
Published: June 2012

Cat heart muscles preserved in normal Tyrode's solution at 4°C for prolonged periods were investigated by recording the transmembrane potentials after rewarming to 37°C. The cell membranes were gradually hyperpolarized during rewarming, the maximum hyperpolarization being reached within a few hours. The amplitude of resting potentials obtained at a maximally hyperpolarized stage was largest for ventricular muscle that had been preserved for 20 hours at 4°C and for atrial muscle that had been preserved for about 50 hours at 4°C. The maximum potentials averaged 267.7 mv for the ventricles and 184.4 mv for the atria. KC1 at 10 x normal and epinephrine and norepinephrine in final concentrations of 2.5 x 10
-7
g/ml brought about a marked hyperpolarization of the cell membrane when the membrane potential of the muscles was declining. The cells of muscles loaded with Li had a greater than normal membrane potential for an hour during gradual equilibration over a range of 4 to 22°C before rewarming. When muscles were rewarmed to 37°C in Li-Tyrode's solution the membrane potential gradually decreased to 5 to 23 mv for the right atrium and 13 to 34 mv for the right ventricle. Ouabain 10
-5
and 10
-6
M abolished the hyperpolarization and subsequently depolarized the cell membrane. DNP (0.2 and 0.6 mM) and sodium azide (6 mM) also had an inhibiting effect on the hyperpolarization. The observations are consistent with a hypothesis of an electrogenic sodium pump, which produces hyperpolarization whose magnitude depends largely on the previous length of time the tissue was preserved in the hypothermic state.
Effect of Ouabain on the ATPase of Cardiac Myosin B at High Ionic Strength
Authors: JACOBSON ADA L.
Published: June 2012

The effect of ouabain (10
-8
to 10
-3
m
) on the hydrolysis of ATP by beef cardiac myosin B was measured at various KC1 concentrations and at various interaction times at 25°C. Using an ionic strength of 0.24
m
KC1 and a 10-minute contact time, 10
-7
and 10
-5
m
ouabain approximately doubled the ATPase activity of freshly prepared natural actomyosin. After storage of the myosin B sample in 0.6
m
KC1 at 2°C, ouabain had a small inhibitory effect in 0.24
m
KC1 on the ATPase activity. At an ionic strength of 0.36
m
KC1, only the inhibitory effect was observed. This effect was dependent on contact time and on calcium ion concentration. Previous treatment of the myosin B with EDTA removed the activating effect observed in 0.24
m
KC1 at short contact times. Addition of 0.1 mM MgCl
2
restored the activating effect of ouabain. In the EDTA-treated myosin B in 0.6
m
KC1 at high ouabain concentrations in the presence of 1 m
m
CaCl
2
, a small activation was observed. Addition of 0.1 m
m
MgCl
2
under the same experimental conditions produced a small deactivation. The effect of ouabain on the ATPase of myosin B in solution appears to be dependent on protein preparation, age of the protein preparation (which may affect aggregation), ionic strength, ouabain concentration, contact time, and divalent ions present. All effects induced by ouabain on the ATPase activity of myosin B may be related to the conformation of the myosin B in solution. However, no simple relationship was observed with any individual variable such as preparation, age, contact time, or ouabain concentration.
Defibrillation without A-V Block Using Capacitor Discharge with Added Inductance
Authors: TOCKER WILLIS A. , GEDDES LESLIE A. , HOFF HEBBEL E.
Published: June 2012

Two hundred and seventy-two defibrillations of the ventricles of 17 dogs by capacitor discharge applied directly to the heart were accompanied by A-V block lasting up to 78 seconds. A range of 150 to 475 volts was employed using a 40 microfarad condenser. The duration of the block was proportional to the energy employed for defibrillation. With the minimum energy of 1.8 watt-sec that produced 100% defibrillation in all trials, A-V block was present in 14 of the 17 animals (average duration of A-V block varying from 3 to 18 seconds). That the A-V block is not vagal in origin was demonstrated by atropinization and vagotomy of the animals. Prolongation of the period of fibrillation up to 15 seconds was found not to be a factor in determining the duration of A-V block. Defibrillation with the same energy levels but with the inclusion of an 0.29 henry inductance abolished the A-V block in 115 defibrillations in the same 17 animals. The current waveform measured without inductance was of the capacitor discharge type (unidirectional and exponentially decaying); with the inductance in the circuit the current waveform was a highly damped sinusoidal alternating current consisting of slightly more than two full cycles of about 40 Hz.
Effect of Nitroglycerin and Dipyridamole on Regional Coronary Resistance
Authors: FAM WADIE M. , MCGREGOR MAURICE
Published: June 2012

We studied the changes caused by intravenous injection of nitroglycerin (0.3 to 0.6 mg) and dipyridamole (5 to 10 mg) on the resistance of large and small coronary arteries of dogs. The direction of change in resistance of large conductive vessels (R
c
) was estimated by dividing the pressure drop from aorta to a superficial branch by the flow in that vessel. The total resistance (R
t
) in the same vessel was estimated by relating aortic pressure to the same flow. The effects of both drugs on aortic pressure were comparable 3 to 7 minutes after injection. Nitroglycerin during this period caused a reduction in R
c
, whereas dipyridamole caused a significant reduction in R
t
for 12 minutes but no consistent changes in R
c
. In the same preparation, small intracoronary doses of the drugs, which hardly affected the aortic pressure, caused comparable changes in resistance. This was also evident in a preparation in which the flow in the coronary vessel was held constant. These two drugs therefore differ in their site of action on the coronary vascular bed, a difference which may explain their contrasting therapeutic effects in chronic coronary disease in man.
Changes in Sodium Balance and Hemodynamics during Development of Experimental Renal Hypertension in Dogs
Authors: CONWAY JAMES
Published: June 2012

After unilateral nephrectomy and application of a Goldblatt clamp to the remaining renal artery, there was sodium retention of approximately 123 mEq in 15 days. At this time, blood pressure increased from 95 to 142 mm Hg without demonstrable changes in plasma volume or cardiac output. When the accumulation of sodium was prevented and a negative balance induced by a low sodium diet and a single dose of a diuretic agent postoperatively, the blood pressure increased from 102 to 139 mm Hg, but it increased further, to 155 mm Hg, after a normal sodium diet had been restored and there had been a gain of 189 mEq of sodium above control. The accumulation of sodium after application of the Goldblatt clamp does not appear to be necessary for the emergence of hypertension, but it does appear to play some part in determining the magnitude of the rise in pressure.
Transmission of Pulsatile Blood Pressure and Flow through the Isolated Lung
Authors: MALONEY JOHN E. , BERGEL DEREK H. , GLAZIER JON B. , HUGHES JOHN M. , WEST JOHN B.
Published: June 2012

A horizontal isolated lung preparation has been used to examine the transmission of pulsatile blood pressure and flow. Arterial and venous pressure and flows were measured with pressure transducers and electromagnetic flowmeters. After a sudden increase in pulmonary arterial pressure, delays of several seconds were observed before venous flow began to increase. Flow then increased slowly over a period of 1 to 9 seconds to a new steady level. The transmission of pulsatile flow was independent of the outlet pressure and identical for perfusion in the forward and reverse directions. Flow transmission fell from about 75% at a frequency of 0.03 cps to approximately 10% at a frequency of 1 cps. Pressure transmission down to the collapsible vessels was measured when alveolar pressure exceeded venous pressure. At 0.1 cps approximately 50% of the incident pressure wave was transmitted, and at 1 cps this was reduced to 30%. It was concluded that the lung passed well only the low-frequency components of the applied input and that in a vertical lung only about 30% of the mean to peak pressure pulse would be transmitted down to the small vessels and therefore affect the distribution of blood flow.
Electrical Excitability of Atrioventricular Nodal Cells
Authors: MERIDETH JOHN , MENDEZ CARLOS , MUELLER WILLIAM J. , MOE GORDON K.
Published: June 2012

The electrical threshold of A-V nodal cells of isolated rabbit heart preparations was estimated by techniques which permitted stimulation and recording through the same micropipette. Cells within the node were significantly less excitable than adjacent atrial and ventricular tissues; thresholds exceeded 5 x 10
-6
amp in some instances. Recovery of excitability was delayed well beyond repolarization; in cells of the midnodal region, "diastolic" threshold was not attained until 0.2 to 0.5 seconds after restoration of resting membrane potential. A cumulative effect of frequency upon excitability (fatigue) was demonstrated. At high driving rates, the lag in recovery was further delayed, and the late diastolic threshold was increased. Responses to single-cell stimulation indicate that summation may be an important feature of propagation within the node.
Distribution of Sympathetic Fibers in the Left Ventricular Epicardial Plexus of the Dog
Authors: GEIS WILLIAM P. , KAYE MICHAEL P.
Published: June 2012

Myocardial contractile force in five areas of the left ventricle was measured in 14 dogs under chloralose anesthesia prior to and following segmental chemical epicardiectomy. Electrical stimulation of the stellate ganglia was performed before and after each segment of epicardium was destroyed, and records of myocardial contractile response to stimulation were obtained. Epicardiectomy resulted in ablation of contractile response in specific areas of the left ventricle. In a recent publication from our laboratory (Circulation Res. 22: 315, 1968), the predominance of an epicardial distribution of sympathetic fibers was demonstrated. As an extension of that work, this study demonstrates the projection of fibers from both left and right stellate ganglia and the innervation of both anterior and posterior surfaces of the left ventricle. The major projections of sympathetic fibers are oriented along an axis passing from base to apex and can be interrupted by epicardial destruction in the area of the cephalad portion of the anterior descending coronary artery and adjacent to the origin of the left marginal artery.
Variations of Left Ventricular End-Diastolic Pressure, Volume, and Ejection Fraction with Changes in Outflow Resistance in Anesthetized Intact Dogs
Authors: TSAKIRIS ANASTASIOS G. , VANDENBERG RUSSELL A. , BANCHERO NATALIO , STURM RALPH E. , WOOD EARL H.
Published: June 2012

Multiple measurements of left ventricular volumes, ejection fractions, and circulatory pressures were made under conditions of varied outflow resistance in five intact anesthetized dogs by using a biplane videoangiographic recording system which displays simultaneously two roentgen images on the same television screen, records the images on video tape, and requires low radiation levels and small amounts of contrast medium. Aortic pressure was controlled by intra-aortic infusion of angiotensin or acetylcholine. With spontaneous sinus rhythm and normal aortic pressure, end-diastolic volume averaged 35 ml (2.3 ml/kg), and ejection fraction averaged 47% of end-diastolic volume. When aortic pressure was increased, average end-diastolic volumes increased to 53 ml and ejection fractions decreased to 29%. Conversely, when aortic pressure was decreased, average ejection fraction increased to 73%, although changes in stroke volume were usually not large under these conditions. Concomitant large changes in the shape of the left ventricular cavity were also observed. Similar changes were observed when heart rate was maintained constant by electrical pacing of the atria and ventricles with a constant atrial-ventricular stimulus interval. The variability in left ventricular volume and ejection fraction observed in the same animal during different circulatory states may account in part for the differences in values for these variables reported by different investigators.
On the Sympathetic Control of Ventricular Automaticity
Authors: VASSALLE MARIO , LEVINE MICHAEL J. , STUCKEY JACKSON H.
Published: June 2012

The effects of stellate ganglion stimulation on idioventricular automaticity were studied in anesthetized dogs. An idioventricular rhythm was obtained in one series of animals by ligating the His bundle and in the other by stimulating the vagus. On isolation of the left stellate ganglion, the idioventricular rate fell by 5 beats/min which is compatible with a rate of "tonic" discharge of about 3 impulses/sec. On stimulation of the stellate ganglia at increasingly higher frequencies, the idioventricular rate accelerated progressively and the frequency-response curve was sigmoid. When the stimulation frequency was increased above 10 to 15 pulses/sec, there was no further enhancement of ventricular automaticity. The ventricular rates attained during sympathetic stimulation rarely exceeded 70/min. The interval between the initiation of sympathetic stimulation and the maximal ventricular acceleration was shorter at higher stimulation frequencies. The effects of right and left stellate stimulation on the rate of idioventricular pacemakers were comparable. Reflex vagal inhibition had little influence on the acceleratory action of the sympathetic nerves on the idioventricular pacemakers since in dogs with atrioventricular block the results before and after vagotomy were similar. Furthermore, the idioventricular rhythm during vagally induced block increased on sympathetic stimulation to values comparable to those obtained in dogs with surgically induced block.
Dual Vasoconstrictor and Vasodilator Innervation of the Uterine Arterial Supply in the Guinea Pig
Authors: BELL CHRISTOPHER
Published: June 2012

The innervation of the extrinsic uterine arterial supply of the guinea pig has been studied using an isolated perfused preparation. The preparation was normally at minimal tone and responded to periarterial stimulation by a vaso-constriction which was mimicked by norepinephrine and abolished by bretylium. Constrictor responses both to stimulation and to norepinephrine were similar in both pregnant and non-pregnant states. In pregnant preparations, raising the tone of the vessels with norepinephrine revealed a powerful dilator response to periarterial stimulation. This response was mimicked by acetylcholine, potentiated by anticholinesterases, reduced by hyoscine, and abolished by-local anesthetic treatment. In contrast, virgin preparations showed only a weak dilator response to stimulation, while the response to acetylcholine even at high concentrations was usually negligible. Histochemical examination of the vessels revealed a dense plexus of fine nerve fibers exhibiting high acetylcholinesterase activity along the main uterine artery. The fibers lay in close apposition to the vascular muscle layer. Nerve fibers exhibited fluorescence for catecholamines were also abundant, but were distributed along the secondary as well as the main arteries. It is concluded that the uterine arterial supply of the guinea pig is innervated by both adrenergic constrictor and cholinergic dilator fibers. The dilator fibers appear to be functional only during pregnancy. The possibility of a noncholinergic dilator innervation is also discussed.
Relationship between Sodium Intake and Norepinephrine Storage during the Development of Experimental Hypertension
Authors: DE CHAMPLAIN JACQUES , KRAKOFF LAWRENCE R. , AXELROD JULIUS
Published: June 2012

It has been reported that storage of norepinephrine by the sympathetic nervous system was decreased in rats made hypertensive by the administration of desoxycorticosterone trimethylacetate (DOCA) and sodium chloride. The present investigation indicated that the storage of norepinephrine was impaired at an early stage of treatment with DOCA and NaCl (1 week), and preceded the appearance of hypertension. The role of sodium and sympathetic activity, the two major factors suspected of contributing to the development of the abnormality in storage of norepinephrine, was studied in normotensive and hypertensive rats. The withdrawal of sodium from the diet of hypertensive rats for 2 weeks lowered the blood pressure to normotensive levels and simultaneously restored to normal the storage and binding capacity as well as the endogenous norepinephrine content of the sympathetic storage granules in the heart. Sodium restriction or depletion in normotensive rats caused a slight decrease in blood pressure and the retention of norepinephrine in the storage granules was increased. These findings suggested that the capacity of the sympathetic granules to bind and store norepinephrine was influenced by the state of sodium balance and showed that the capacity of storage could be correlated with the level of blood pressure. The finding that treatment with a long-acting ganglionic blocker could restore the blood pressure and the norepinephrine storage capacity in hypertensive animals to normal suggested a neurogenic component in the development of this form of hypertension.
Inhibition of Renin Release in the Dog by Vasopressin and Vasotocin
Authors: VANDER ARTHUR J.
Published: June 2012

In anesthetized dogs the intravenous infusion of arginine vasotocin, 25 mU/min, or vasopressin, 10 mU/min, inhibited renin secretion when control secretion rates were normal or when they were elevated by complete ureteral occlusion. Vasotocin, 5 mU/min, or vasopressin, 1 mU/min, was ineffective. Direct intraarterial infusion of vasotocin, 5 mU/min, into the right kidney inhibited renin secretion by the right kidney only. Glomerular filtration rate and renal plasma flow were not changed, and mean arterial pressure was either not changed or was decreased. Vasotocin caused no change in urine flow but did produce a significant natriuresis secondary to decreased tubular reabsorption. The physiological implications of these polypeptide-renal relationships are discussed.
Investigation of the Hepatic Arterial "Space" under Various Conditions of Flow in the Isolated Perfused Dog Liver
Authors: FIELD C. D. , ANDREWS W. H.
Published: June 2012

A radioactive isotope dilution technique, in which two radioactive tracers were used simultaneously, was employed to investigate the nature of the hepatic arterial vascular bed or arterial vascular "space" in 22 isolated perfused canine livers. The technique continuously monitored the blood leaving the liver for radioactivity so that no assumptions had to be made regarding the representative nature of samples. The concept of an arterial vascular space was defined in terms of the mean circulation time of labeled red cells through the perfused organ, and the variation of this parameter with variations in arterial flow was considered; agreement with other published work was shown. The experiments on the size of the arterial vascular space showed a linear relationship between the arterial fraction of the blood occupying the total hepatic vascular bed and the arterial fraction of the total hepatic blood flow. The evidence from these experiments supported the idea that the artery and the portal vein share a large proportion of the total hepatic vascular bed.
Peripheral Mechanism Involved in Response of Dogs' Cutaneous Veins to Local Temperature Change
Authors: WEBB-PEPLOE MICHAEL M. , SHEPHERD JOHN T.
Published: June 2012

The cutaneous veins of the dog constrict and dilate with local cooling and warming, respectively. This response, which is dependent on the integrity of the adrenergic nerves, might be explained by an altered response of the smooth muscle to a given frequency of sympathetic nerve impulses or by local temperature receptors that initiate alterations in sympathetic nerve activity. In the lateral saphenous vein perfused at 42°, 27°, and 17°C, the constriction caused by stimulation of lumbar sympathetic nerves was 40%, 160%, and 200%, respectively, of that at 37°C; the constriction caused by norepinephrine at the same temperatures was 70%, 187%, and 318% of that at 37°C. Division of the dorsal spinal roots from L-1 to S-1 made no difference to the veno-constrictor response to local cooling. It is concluded that an alteration in the sensitivity of the smooth muscle to arriving sympathetic nerve impulses accounts for the venous responses to local temperature changes seen in the intact dog.
Effect of Thyroid Hormone on the Frequency-Force Relationship of Atrial Myocardium from the Guinea Pig
Authors: MURAYAMA MASAHIRO , GOODKIND M. JAY
Published: June 2012

Measurements of the frequency-force relationship were made in left atrial muscle from euthyroid and hyperthyroid guinea pigs and the effects of calcium and norepinephrine on this relationship examined. Isometric contractile force was measured with the muscle suspended in a bath of Krebs-Henseleit solution oxygenated by a gas mixture of 95% O
2
-5% CO
2
at 28°C. Frequency of stimulation was varied from 0.5 to 200/min at suprathreshold voltage delivered by plate electrodes. Low frequency stimulation caused less of a negative inotropic effect in hyperthyroid than in normal controls. The maximum negative and positive inotropic effects in the thyroxine-treated guinea pigs occurred at lower frequencies than in normal controls. These changes altered the shape of the myocardial frequency-force curve of hyperthyroid animals from that of normal controls. Norepinephrine and calcium in the dose levels examined produced a smaller than normal increment in the developed tension of hyperthyroid animals, but the maximum developed tension was similar in the two groups of animals. The lack of effect of reserpine on the frequency-force curve of left atrial muscle from hyperthyroid animals suggests that endogenous norepinephrine stores are not necessary for the production of a change in the curve. The alteration in the frequency-force relationship of atrial muscle from hyperthyroid guinea pigs is further evidence of a direct effect of thyroid hormone on the myocardial contractile mechanism.
Microelectrode Study of Delayed Conduction in the Canine Right Bundle Branch
Authors: WENNEMARK JAMES R. , RUESTA VICTOR J. , BRODY DANIEL A.
Published: June 2012

The electrophysiology of conduction delay was investigated in the semi-isolated right bundle branch of 30 large mongrel dogs. Delay was produced by the external application of an electric blocking current to the bundle branch. Multiple recordings with glass capillary microelectrodes revealed two basic deflections associated with the delay phenomenon. An initial, or leading, deflection originated from the proximal or leading edge of the block and was rapidly transmitted through the block with progressive decay of voltage and rise velocity. A second, or trailing, deflection originated from the regenerative response at the distal or trailing edge of the block and was rapidly transmitted retrograde into the block, with progressive decay of voltage and rise velocity. The transmitted potentials appeared to be electrotonic in nature.

The leading deflection appeared to be the transmitted event which maintained a conduction ratio of 1:1 through the block. The magnitude of delay was then related to the time required for this deflection to reach the threshold potential and initiate a regenerative response in the trailing portion of the block where the cells were less affected by the blocking current.
The Elastic Symmetry of Arterial Segments in Dogs
Authors: PATEL DALI J. , FRY DONALD L. , Janicki Joseph S.
Published: June 2012

Elastic symmetry was studied in the middle descending thoracic aorta, abdominal aorta, and left common carotid artery under physiologic ranges of loading in ten dogs. A segment of the blood vessel was isolated and hung vertically. As the segment was pressurized, the radius, length, and the rotation of the lower end of the vessel were measured with respect to the fixed upper end. In addition, the angular displacement of a glass whisker initially placed perpendicularly through the wall was measured. From these data it was possible to calculate the values of shearing strains and elongating strains associated with pressurization and various imposed longitudinal stresses. The values of shearing strain varied from 0.003 to 0.115 over pressure ranges of 3 to 270 cm H
2
O. In all instances the values of shearing strain were much smaller than the corresponding elongating strains. It was concluded that the vessel has elastic properties that are nearly symmetrical about the planes perpendicular to principal stresses under physiologic loading, i.e., the vessel may be treated as a cylindrically orthotropic tube.