bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of Coronary Vasodilating Action of ATP and Adenosine by Lidoflazine
Authors: AFONSO SKODA , O'BRIEN GEORGE S. , CRUMPTON CHARLES W.
Published: June 2012

Lidoflazine, a newly developed coronary vasodilator, greatly enhances the coronary vasodilating action of adenosine and ATP. Experiments were designed to study the combined coronary vasodilating effects of adenosine and lidoflazine and to quantify the enhancement of coronary vasodilation of adenosine and ATP by prior administration of lidoflazine. Results of the experiments showed that the combined coronary vasodilating effects of adenosine and lidoflazine can be classified as supra-additive. For 3 hours after the administration of lidoflazine there was a great intensification (20 to 150 times) of the vasodilating action of adenosine or ATP. An adenosine-sparing effect of lidoflazine in whole blood was also demonstrated, and the enhancement of adenosine action is in part related to this effect. It is suggested that lidoflazine may also produce a change in the sensitivity of the smooth muscle of the coronary vessels to the direct or indirect action of adenosine.
Contribution of Kinins to Endotoxin Shock in Unanesthetized Rhesus Monkeys
Authors: NIES ALAN S. , FORSYTH RALPH P. , WILLIAMS HIBBARD E. , MELMON KENNETH L.
Published: June 2012

The effects of endotoxin (
Escherichia coli
and
Pseudomonas pseudomallei
) were studied in 18 unanesthetized rhesus monkeys restrained in primate chairs. Indwelling arterial and venous catheters were used for hemodynamic measurements and blood sampling. Whole blood kinin, plasma kininogen, lysosomal enzymes, complete blood counts, and blood gas tensions were measured. Within an hour of beginning the infusion of the endotoxin, the mean arterial pressure and systemic peripheral resistance decreased significantly in the 18 experimental monkeys compared to 13 control monkeys. These early changes were associated with significant elevation in whole blood kinin concentration and a decrease in plasma kininogen. All of these early changes were most marked in the animals that died. Granulocytopenia occurred within 15 minutes, and the concentration of free lysosomal enzyme in the plasma rose 2 hours after endotoxin infusion. The preterminal phase of shock was characterized by a low peripheral vascular resistance and decreasing cardiac output without elevation of kinin levels. These findings support the hypothesis that kinins play a pathogenetic role in the early phase of endotoxin-induced shock and that the severity of the early phase may influence the animal's survival. The relation of kinins to other vasoactive substances released after endotoxin-induced shock is unknown.
Electrophysiological Effects of Diphenylhydantoin on Canine Purkinje Fibers
Authors: BIGGER J. THOMAS , BASSETT ARTHUR L. , HOFFMAN BRIAN F.
Published: June 2012

The effects of diphenylhydantoin (DPH) were studied on isolated, perfused Purkinje fibers over a range of concentrations from 10
-8
to 10
-4
M
. The time course of repolarization of the transmembrane action potential shortened due to abbreviation of all phases of repolarization. The effective refractory period also shortened during exposure to DPH, but to a lesser extent than the action potential. As a result the earliest effective test stimulus elicited action potentials with greater amplitude and dv/dt of phase 0 than under control conditions. In driven fibers with normal action potentials, DPH had little effect on the amplitude or rate of rise (dv/dt) of phase 0 of the action potential. In driven fibers which were partially depolarized, or those with low dv/dt of phase 0 despite normal resting potentials, DPH caused an increase in the rate of rise of phase 0 of the action potential. DPH caused a decrease in the firing rate of normal automatic fibers by decreasing the slope of phase 4 depolarization. In automatic fibers which showed generalized diastolic depolarization and decreased maximum diastolic potential, DPH caused an increase in the latter as well as a decrease in the slope of phase 4 depolarization.
Interstitial Fluid Pressure
Authors: MEYER BERNARD J. , MEYER ALETTA , GUYTON ARTHUR C.
Published: June 2012

Interstitial fluid pressures in the lung were estimated in 39 dogs from pressure measurements made in implanted perforated capsules. Special operative procedures were used to minimize operative trauma of the lungs and infection and inflammation in and around the implanted capsules. In 86% of the preparations, the x-ray findings indicated little remaining inflammation and edema around the capsules, though autopsy findings indicated that a few of these did still have some edema not detectable by x-rays. In 29 of 34 animals in which x-ray findings indicated no edema, the intracapsular pressure was negative. The average of the measurements in all 34 animals was -5.8 mm Hg (± 0.8
SEM
), and in the 29 animals with negative pressure values the average was -7.3 mm Hg (± 0.6
SEM
). In eight capsules the pressures were below -10 mm Hg, ranging to -16 mm Hg. Because the tissues around some of the capsules undoubtedly still had varying degrees of inflammation and edema, despite the failure of roentgenograms to show these, it is suggested that the normal interstitial fluid pressure of pulmonary tissues in dogs is somewhat more negative than the capsule pressure measurements indicate, perhaps as low as -10 mm Hg.
Left Ventricular Pressure-Volume Relations and Performance as Affected by Sudden Increases in Developed Pressure
Authors: MONROE R. G. , LA FARGE C. G. , GAMBLE W. J. , ROSENTHAL A. , HONDA S.
Published: June 2012

Left ventricular performance in the isolated dog heart was observed in a preparation in which left ventricular pressure and volume could be monitored continuously while the ventricle contracted isobarically by compressing air into a large chamber. By suddenly reducing the orifice connecting the ventricle to the chamber a constant load was imposed on the ventricle, abruptly forcing it to develop pressure in systole. This pressure increased over the ensuing 3 minutes while both the load and the end-diastolic pressure remained constant, implying that the sudden development of pressure by the ventricle was attended by a positive inotropic effect, otherwise known as homeometric autoregulation. Further studies showed this positive inotropic effect to be a function of the magnitude of the abrupt increase in systolic pressure and the time course of the experiment. β-adrenergic receptor blockade with propranolol decreased but did not abolish this effect. Infusion of norepinephrine did not enhance it. Increases in ventricular compliance that accompanied loading could not fully account for it. Evidence is presented that this positive inotropic effect may in part be mediated through the release of intrinsic catecholamines when the ventricle is forced to increase its systolic pressure.
Role of Histamine in Hypoxic Pulmonary Hypertension in the Rat
Authors: HOUGE ANTON
Published: June 2012

Pharmacological agents that block or potentiate the effects of naturally occurring vasoactive substances were used to try to determine which substance, if any, mediates the vasoconstrictor response to acute alveolar hypoxia in isolated rat lungs. Isolated and ventilated lungs of rats were perfused at 37°C with homologous blood at constant-volume, pulsatile inflow, and pressor responses to brief periods of ventilation hypoxia (2% O
2
) were recorded (control, 21% O
2
). Antihistamines of four different chemical classes in concentrations of 70 to 140 µg/ml abolished all pressor responses to alveolar hypoxia without interfering with the effects of injected bradykinin, ATP, or serotonin. A histaminase-inhibiting compound, semicarbazide, potentiated the hypoxic pressor response. The hypoxic pressor response could not be abolished by α-receptor-, serotonin-, or ATP-blocking agents. The results suggest that endogenous histamine in the lung is involved in the vasoconstrictor response to acute alveolar hypoxia.
Renin Release
Authors: NASH FRANKLIN D. , ROSTORFER HOWARD H. , BAILIE MICHAEL D. , WATHEN RONALD L. , SCHNEIDER EDWARD G.
Published: June 2012

The relations between renin release and renal hemodynamics, renal sodium load, and sodium and water balance were studied during hyponatremia, hypernatremia, mercurial natriuresis, norepinephrine infusion, and reduction in renal perfusion pressure. Significant reciprocal relations were found between renin secretory activity and the renal arterial plasma sodium concentration, the filtered sodium load, and urinary sodium excretion; however, no significant, or even consistent, relations were found between renin release and any hemodynamic parameter or sodium or water balance. During bilateral stimulation of renin release, unilateral restoration of the filtered sodium load inhibited ipsilateral renin release, without demonstrable changes in hemodynamics, while renin release from the contralateral kidney continued unabated. However, this inhibition was not seen unless the filtered sodium load and urinary sodium excretion rose to control levels even though renal venous plasma sodium concentrations exceeded 170 mEq/liter. Thus, renin release can be dissociated from hemodynamics and sodium and water balance, but not from some function of the filtered sodium load. We propose that renin secretory activity is controlled by an intrarenal, but extravascular, sodium-sensitive mechanism and that the stimulus is a function of the sodium flux across the macula densa into the interstitium surrounding the contiguous juxtaglomerular cells.
Observations on the Mechanism of Emetine Poisoning of Myocardial Tissue
Authors: BELLER BARRY M. , Mongillo Stephen
Published: June 2012

The effect of emetine hydrochloride on protein synthesis in rat myocardium was studied. Emetine inhibited incorporation of tritiated leucine into soluble proteins and actomyosin in an in vitro system using minced rat myocardium in a supporting medium. Fifty percent inhibition of incorporation of the isotope into soluble proteins and actomyosin occurred at an emetine concentration of 5 x 10
-7
M. Incorporation was also significantly inhibited when animals were treated with emetine for three days. The data suggest that emetine toxicity in the myocardium may be mediated through its effects on protein biosynthesis.
Effect on Left Ventricular Performance of Stimulation of an Afferent Nerve from Muscle
Authors: MITCHELL JERE H. , MIERZWIAK DONALD S. , WILDENTHAL KERN , WILLIS WILLIAM D. , SMITH ALVIN M.
Published: June 2012

The effect on left ventricular performance of electrical stimulation of the cut central end of the quadriceps nerve was studied in open-chest dogs. Stimulation of the nerve at 2 to 4 times threshold for the flexion reflex, which presumably activated intermediate-sized afferent fibers, caused a decrease in heart rate and arterial pressure. Stimulation at 5 to 25 times threshold, which presumably activated small-sized, high-threshold afferent fibers, increased heart rate, arterial pressure, and cardiac output. When heart rate, arterial pressure, and cardiac output were controlled, activation of high-threshold afferent fibers caused a significant increase in the maximal rate of pressure rise, stroke power, and mean rate of ejection of the left ventricle without an increase in the end-diastolic pressure. These same fibers may in some way be activated during muscular exercise and be partially responsible for the increase in left ventricular contractility that occurs during that time.
Cardioglobulin
Authors: HAJDU STEPHEN , MAXIMIN T. J. , LEONARD EDWARD J.
Published: June 2012

Cardioglobulin is a protein system in mammalian plasma, assayed by its effect on contractility of isolated frog heart. Gel filtration was employed to separate individual components, called cardioglobulin-A, -B and -C, from rat and human plasma: Cardioglobulin-A of both rat and human is a small globulin. Biological activity is abolished by heparin. A part of rat plasma cardioglobulin-A probably exists as a readily dissociable complex with another protein and is not inactivated by heparin. Rat cardioglobulin-C is a large globulin, contains calcium essential for biological activity, and binds strongly to the frog heart. The human protein that corresponds functionally to rat cardioglobulin-C is a much smaller globulin and does not bind. Both rat and human cardioglobulin-B are sensitive to heparin at concentrations recommended for collection of plasma but are stable in tenfold lower concentrations that still prevent clotting. Human cardioglobulin-B separates into two fractions on G-200 Sephadex. It is not known whether they exist as a complex in plasma or as individual proteins. Rat cardioglobulin-B has not been isolated, but preliminary data indicate it is chemically distinct from human cardioglobulin-B. As a result of this work, assay of individual Cardioglobulin components can be reliably performed.
Sites of Impulse Formation within the Atrioventricular Junction of the Rabbit
Authors: WATANABE YOSHIO , DREIFUS LEONARD S.
Published: June 2012

Spontaneous A-V nodal rhythm was observed in 23 isolated, perfused rabbit hearts during electrophysiologic studies of A-V transmission. In 19 of the 23, the earliest point of activation was determined by recording transmembrane potentials from numerous A-V junctional fibers. Most commonly (15 hearts), the earliest depolarization was found in a specific area of the A-V node near the point where the fibrous A-V ring extending into the coronary sinus joins a portion of A-V ring between right atrial and ventricular free walls. Various observations suggested that this area was the NH region. In the remaining four hearts, the origin of nodal beats was in the AN region. Diastolic depolarization was often seen in and around the earliest point of activation. The A-V interval in these nodal rhythms ranged from -38.7 to +71.6 msec, in contrast to the A-V interval of 93.3 to 135.7 msec during sinus rhythm. In the presence of NH rhythm, different retrograde intranodal conduction time (across the N region) was the major cause for the wide variation of the A-V interval. Wandering of the pacemaker between the S-A and A-V nodes and examples of exit block of A-V nodal impulses were observed.
Glucagon
Authors: GLICK GERALD , PARMLEY WILLIAM W. , WECHSLER ANDREW S. , SONNENBLICK EDMUND H. , Lewis Robert M. , McGill Richard D.
Published: June 2012

The action of glucagon on cardiac performance was studied in 21 isolated cat papillary muscle preparations, in 13 spontaneously beating cat atria, in 15 intact dog hearts, and in 4 isolated perfused dog hindlimbs. In each papillary muscle preparation, addition of glucagon produced marked increases in maximal developed tension, averaging 36±4.2% (
SEM
) (
P
< 0.01), and shifted the force-velocity curve upwards and to the right, indicating that contractility was augmented. Glucagon always increased the rate of the spontaneously beating atrium, the rise averaging 28.8±5.5 contractions/min (
P
< 0.01). In the dog, myocardial performance was markedly augmented by the administration of glucagon, 50 µg/kg iv, as indicated by an average increase of 72.2±18.4% (
P
< 0.01) in the left ventricular peak dP/dt and of 58.9±12.8% (
P
< 0.01) in force recorded by a strain gauge arch, despite an average decrease of 3.8±1.2 cm H
2
O (
P
< 0.02) in left ventricular end-diastolic pressure. Heart rate rose an average of 38.7±10.9 beats/min (
P
< 0.02). Small but significant decreases in peripheral vascular resistance were produced. Single intravenous injections produced effects lasting 15 to 20 minutes. Propranolol did not prevent the inotropic responses in either the cat or dog preparations but markedly decreased the chronotropic effects.
Ribonucleic Acid Synthesis in Experimental Cardiac Hypertrophy in Rats
Authors: POSNER BARRY I. , FANBURG BARRY L.
Published: June 2012

The sequence of events which lead to increased RNA synthesis in the heart following aortic constriction was studied with the use of inhibitors of protein and RNA synthesis. Puromycin given during the first 4 hours after operation inhibited the increase in RNA labeling with [
32
P] H
3
PO
4
that occurred after 4 hours of aortic constriction without inhibiting RNA labeling in sham-operated rats. Puromycin had no effect on the
32
P labeling of the alpha-phosphate of AMP which suggests that the effect on labeling of RNA is not mediated by the lowering of precursor specific activity. The dose of puromycin used inhibited the labeling of heart muscle protein with
3
H leucine. Parafluorophenylalanine had no selective inhibitory effect on the increase of RNA labeling in the hypertrophying heart.

The most likely interpretation of these data is that, following aortic constriction, synthesis of protein is required for subsequent stimulation of RNA synthesis, and this protein may be dependent upon the synthesis of new RNA templates. Any early increased synthesis would be of a minority species of protein since there was no increase in amino acid labeling of total heart protein until 4 to 6 hours after aortic constriction.

The stimulation of RNA labeling by aortic constriction was unaffected by digitalis treatment. The pressure-time index did not correlate with the increased labeling of RNA.
Estimation of Coronary Blood Flow by Washout of Diffusible Indicators
Authors: BASSINGTHWAIGHTE JAMES B. , STRONDELL TORE , DONALD DAVID E.
Published: June 2012

In 13 canine hearts, 158 disappearance curves for
133
Xe and antipyrine-1
125
I, given by intra-arterial slug injection, were recorded at a wide range of perfusion rates. Flow rates (ml/100 g/min) calculated from these curves by a variety of methods were compared with measured flow rates (F
a
) per weight of perfused tissue. Perfusion of isolated, supported hearts and of anterior descending coronary arteries in open-chest dogs provided similar data. The semilogarithmic slope of curves from apex or whole heart decreased with time, particularly at high flow rates. There was a small, consistent difference in shape between antipyrine and xenon curves, suggesting that radioactivity in fat contributed somewhat to this tailing. Estimation of flow rate from the steepest semilog slope yielded an average value of 1.1 F
a
for all rates; estimation from slope at 30% of peak radioactivity gave 0.9F
a
. The curves were closely described by a two-exponential equation which gave flow estimates of 0.95F
a
when collimation limited the observations to the heart apex, and lower values when the whole heart was observed. Peak height/area methods gave values of approximately 0.75F
a
in spite of various compensations for the impossibility of recording the curve until radioactivity = 0.
Some Mechanical Properties of Isolated Mammalian Cardiac Muscle
Authors: HOFFMAN BRIAN F. , BASSETT ARTHUR L. , BARTELSTONE HERBERT J.
Published: June 2012

Isolated preparations of mammalian cardiac muscle have been employed to study possible mechanisms responsible for changes in diastolic compliance. Muscles have been studied at rest and during isometric and afterloaded contractions, at fixed initial length and during programmed, cyclic changes in length, and under the influence of paired stimulation, catecholamines, and elevated extracellular calcium concentrations. The results obtained indicate that, although there is a series viscous element in cardiac muscle, which accounts for stress-relaxation, some changes in compliance apparently result from alterations in the extensibility of the contractile element. This conclusion is based primarily on experiments showing shifts in the apex of the length-tension curve produced by action of inotropic agents which alter diastolic compliance and on experiments showing that the rate and extent of relaxation of afterloaded contractions depend on the extent of shortening during contraction.
Relationship between Intrarenal Hydrostatic Pressure and Hemodynamically Induced Changes in Sodium Excretion
Authors: MARTINO JOSEPH A. , EARLEY LAURENCE E.
Published: June 2012

Deep intrarenal venous pressure was used as an index of renal capillary pressure to test the proposal that physically induced changes in sodium reabsorption may be mediated by changes in Starling forces across the capillary. Renal vasodilatation produced natriuresis associated with immediate increases in intrarenal venous pressure. Increased arterial pressure was accompanied by further natriuresis and initially increased intrarenal pressure in vasodilated kidneys. Plasma load was always accompanied by increased intrarenal venous pressure. Saline loading usually increased intrarenal venous pressure, and restoration of plasma protein concentration during saline loading reduced, but did not abolish, natriuresis. This continued natriuresis was associated with reduced renal vascular resistance and increased intrarenal venous pressure, demonstrating that continued natriuresis after restoring plasma oncotic pressure during saline loading could relate to increased capillary hydrostatic pressure. Intrarenal venous pressure did not relate to isolated changes in urine flow, arterial pressure, or renal blood flow. These observations support the hypothesis that changes in peritubular capillary hydrostatic pressure initiate changes in tubular sodium reabsorption as a result of changes in capillary uptake.
Observations on the Regulation of Arterial Blood Pressure in Unanesthetized Dogs
Authors: LAMBERTI JOHN J. , URQUHART JOHN , SIEWERS RALPH D. , Pearson Charles
Published: June 2012

Aortic pressure rises as a dog's head is raised and falls as it is lowered. Systemic pressure change was 49%±3% of the hydrostatic pressure change at the carotid sinus, chosen as an arbitary reference, so that pressure at the carotid sinus changed only 51% as much as it would have if systemic pressure had not changed. The responses to head raising and lowering were dynamically asymmetrical, in a way which permits them to be described as being dependent on the rate of head lowering as well as on vertical position. When chloralose-anesthetized dogs maintained with positive-pressure breathing were studied under water, the response was abolished, suggesting its hydrostatic basis. Chronic carotid baroreceptor deafferentation or carotid sinus excision only diminished the response to changes in head position in most animals, and a transient response to head lowering persisted in all. An apparent CNS adaptation to the disruption of baroreceptor afferents makes it impossible to judge the quantitative role of the carotid sinus reflex in the relation of head position to blood pressure in intact dogs. The effect of head motion on blood pressure are predictable in a model of blood pressure control basedon the known dynamic relations between carotid sinus and systemic pressures, from which we tentatively conclude that vertical head motion acts on blood pressure through the carotid sinus reflex. If so, the measurement of vascular responses to head motion can serve as a nondestructive, quantitative test of baroreceptor reflex dynamics in intact, unanesthetized animals.
Isolation from a Salivary Gland of Granules Containing Renin and Kallikrein
Authors: CHIANG TZU S. , ERDÖS ERVIN G. , MIWA ISAO , TAGUE LARRY L. , COALSON JACQUELINE J.
Published: June 2012

Granules of the submaxillary gland of the white mouse contain both kallikrein and renin. The granules were separated and concentrated in sequential centrifugation procedures. They were more stable at room temperature and in hypertonic sucrose solutions than in the cold or in isotonic solution. The amylase, acid phosphatase, renin, kallikrein, and benzoyl-L-arginine ethyl ester esterase contents of the granules were determined. Kallikrein and renin showed a similar distribution pattern after fractionation. Granular renin released the equivalent of 9.6 µg angiotensin II amide/mg enzyme protein/min from swine serum angiotensinogen. Granular kallikrein liberated from human kininogen the equivalent of 8.4 µg bradykinin/mg enzyme protein/min.

Electron micrographs of the isolated granules showed various forms; some were spherical and symmetrical, and others were amorphous.
Pressure Wave Transmission along the Human Aorta
Authors: O'ROURKE MICHAEL F. , Blazek James V. , Morreels Charles L. , Krovetz L. Jerome
Published: June 2012

Pressure waves were recorded in the proximal aorta, iliac artery, and intermediate sites in 39 patients, aged 6 to 69 years, during diagnostic catheterization. In children, amplitude of the pressure wave increased progressively along the aorta, and a prominent diastolic wave appeared in the distal aorta and iliac artery. These changes in contour were associated with fluctuations in modulus and phase of the pressure wave harmonics. Alterations in the pressure wave during transmission became progressively less with increasing age, and the wave was transmitted virtually unchanged in the older patients with arterial degenerative disease. Percentage amplification (A) of the wave between aortic arch and iliac artery and age (x) were inversely related (A = 58.9 - 0.90x;
P
<0.001). Transmission time (T, msec) from diaphragm to iliac artery shortened with age (T = 63.5 - 0.62x;
P
<0.001) indicating a decrease in arterial distensibility. The relationship between amplification and transmission time in the abdominal aorta and iliac artery was A = 1.04T - 16.7 (P< 0.001). Findings are attributed to a decline in peripheral reflection coefficient resulting from decreased distensibility of peripheral arteries with age and in arterial degenerative disease. The functional effects of decreased distensibility are to impair the efficiency of the arterial system in accepting pulsatile flow, and so to increase the load presented to the left ventricle.
Calcium Uptake Activity of Canine Myocardial Sarcoplasmic Reticulum in the Presence of Anesthetic Agents
Authors: LAIN RICHARD F. , HESS MICHAEL L. , GERTZ EDWARD W. , BRIGGS F. NORMAN
Published: June 2012

The anesthetics chloroform, halothane, ethyl ether, and sodium pentobarbital, which have negative inotropic properties, were examined for effects on the calcium pump of the sarcoplasmic reticulum of the dog myocardium. Chloroform and sodium pentobarbital, at concentrations similar to those depressing cardiac contractility, inhibited calcium uptake. The concentration of halothane required to inhibit calcium uptake was ten times greater than that required to produce depression of contractility. Ether at concentrations eight times greater than those producing inhibition of contraction was completely without effect on calcium uptake. Chloroform and halothane depressed calcium uptake and calcium-stimulated ATPase activity in parallel, indicating that these agents do not uncouple transport from ATP hydrolysis. Sodium pentobarbital, in contrast, uncoupled transport from ATP hydrolysis.
Catecholamines in Arteries and Veins of the Foreleg of the Dog
Authors: MAYER HOWARD E. , ABBOUD FRANCOIS M. , BALLARD DENNIS R. , ECKSTEIN JOHN W.
Published: June 2012

The catecholamine content of various blood vessels of the foreleg of the dog was measured by a fluorimetric method (48 vascular segments from 11 dogs) and also by bioassay (33 segments from 8 dogs). The results obtained by the fluorimetric method indicate that the average concentration of catecholamines in the brachial artery (0.14 µg/g of wet tissue) was significantly lower than that in the ulnar (0.70 µg/g) and metacarpal arteries (0.66 µg/g); the average concentration in the brachial vein (0.17 µg/g) was significantly lower than that in the cephalic (1.30 µg/g) and metacarpal veins (0.47 µg/g). The values obtained by bioassay were generally higher than those obtained by the fluorimetric method, but the differences between the arterial segments and between the venous segments were similar by both methods. There was a close correlation between the concentration of catecholamines in the different vascular segments and the relative responsiveness of these segments to nerve stimulation as reported previously (Circulation Res. 18: 263, 1966). Pretreatment with reserpine decreased markedly the catecholamines in segments of ulnar artery and cephalic vein. Intravenous infusion of norepinephrine in amounts sufficient to raise blood levels of catecholamines five- to tenfold did not alter the content of segments of ulnar artery.
Increased Cardiovascular Reactivity Caused by Depletion of Endogenous Renin in Dogs
Authors: BUNAG RUBEN D. , MCCUBBIN JAMES W. , PAGE IRVINE H.
Published: June 2012

Increase in cardiovascular reactivity following bilateral nephrectomy has previously been found to be independent of the presence of the central nervous system, mechanical exclusion of the renal vascular bed, or loss of renal excretory function. It was considered possible that increased responsiveness results from removal of endogenous stores of renin. In nephrectomized dogs treated with crude kidney extracts, or infused continuously with synthetic angiotensin for 48 hours, enhancement of response to angiotensin and renin was inhibited while that to norepinephrine was not; response to tyramine was augmented as after infusion of angiotensin into intact dogs. Treatment with liver extracts alone did not inhibit response to renin or angiotensin; neither did continuous infusion of norepinephrine. When hog renin was added to liver extracts, the combination had the same inhibitory effect as kidney extracts. The data are in accord with the concept that depletion of endogenous renin contributes to the enhanced pressor responsiveness that occurs following bilateral nephrectomy.
Cardiac Inotropic and Coronary Vascular Responses to Countershock
Authors: COBB FREDERICK R. , WALLACE ANDREW G. , WAGNER GALEN S.
Published: June 2012

These experiments were designed to examine the role of excitation of intracardiac nerves in the response to countershock with either alternating current (ac) or direct current (dc). Studies were performed on intact anesthetized dogs and on isolated perfused hearts. In intact dogs a-c and d-c countershock produced transient sinus arrest and an increase in myocardial contractile force. Sinus arrest could be prevented with atropine, and the positive inotropic response could be prevented with propranolol or prior surgical denervation of the heart. In isolated hearts, a-c and d-c countershock produced sinus arrest which could be prevented with atropine or hemicholinium-3. Alternating-, but not direct-, current countershock increased contractile force of the isolated heart. The inotropic response to ac could be blocked with propranolol and was absent in hearts removed from dogs which had undergone prior cardiac denervation. Both a-c and d-c countershock produced a decrease in coronary vascular resistance which could be prevented with atropine. Cholinergic responses to countershock persisted after surgical denervation of the heart. These observations provide evidence for excitation of intracardiac cholinergic and adrenergic nerves by countershock. Direct-current countershock excites cardiac sympathetic nerves in intact dogs, but not in isolated hearts. Intracardiac cholinergic nerves persist after surgical denervation of the heart.
Incorporation of Oleic Acid into Lipid by Foam Cells in Human Atherosclerotic Lesions
Authors: WAHLQVIST MARK L. , DAY ALLAN J. , TUME RONALD K.
Published: June 2012

The incorporation of
14
C-labeled oleic acid into phospholipid, cholesterol ester, and triglyceride in human arterial intima (normal and atherosclerotic) obtained from kidney transplant donors has been investigated in vitro. Most of the oleic acid was incorporated into phospholipid, in both the normal intima and the atherosclerotic lesion, but a greater proportion of label was diverted to cholesterol ester in the lesion. Representative sections of the vessels used for metabolic studies were taken for radioautography, and these demonstrated localization of
14
C to foam cells, but very little localization in the region of spindle-shaped cells. It was concluded that lipid synthesis in the human atherosclerotic lesion takes place predominantly in the intimal foam cells.
Development of the Action Potential of the Prenatal Rat Heart
Authors: COUCH JAMES R. , WEST THEODORE C. , HOFF HEBBEL E.
Published: June 2012

Transmembrane action potentials were recorded from embryonic rat hearts at ages between 10½ days of gestation and birth (21 to 22 days). The resting potential averaged 30 to 40 mv at 10½ days and increased to around 80 mv by birth. Two periods of rapid increase in resting potential were noted: 1) from 10½ to 13½ days and 2) from 19½ days of gestation to birth. The maximal upstroke velocity of the action potential increased as the resting potential increased. The duration of the ventricular and atrial action potentials was inversely related to heart rate, and their rate sensitivity decreased with age. The atrial action potential lost its rate sensitivity by 13½ days of gestation and the ventricular action potential lost its by birth. At 10½ days diastolic depolarization was found in the area of the ventricle proximate to the A-V junction, the left and right atria, and the sinus venosus. The velocity of the diastolic depolarization was greatestin the sinus venosus and least in the ventricle. The diastolic depolarization decreased with growth and was lost by 13½ days of gestation.
Factors Contributing to the Reversible Pulmonary Hypertension of Patients with Acute Respiratory Failure Studied by Serial Observations during Recovery
Authors: ABRAHAM A. S. , COLE R. B. , GREEN I. D. , HEDWORTH-WHITTY R. B. , CLARKE S. W. , BISHOP J. M.
Published: June 2012

Eight patients with acute respiratory failure secondary to chronic bronchitis were studied for up to 5 consecutive days following admission; cardiac output and intravascular pressures, blood volume, arterial blood gas tensions, and body weight were measured. These observations were also compared with further measurements made some weeks later just before the patient was discharged. The effects of oxygen and acetylcholine on the pulmonary circulation were also studied. Pulmonary arterial pressure was raised in all patients during their acute illness and had fallen substantially after recovery. The pulmonary arterial pressure throughout the study correlated directly with the arterial carbon dioxide and inversely with the arterial oxygen tensions. The inhalation of 24% and 28% oxygen and the infusion of acetylcholine into the pulmonary artery resulted in a fall in pulmonary arterial pressure, often to levels close to those subsequently seen after recovery from the acute illness. No significant change in cardiac output was observed. It is suggested that the acute pulmonary hypertension seen in these patients is due primarily to pulmonary vasoconstriction resulting from hypoxia.
Fine Structural Localization of Acetylcholinesterase at a Cholinergic Vasodilator Nerve-Arterial Smooth Muscle Synapse
Authors: BELL CHRISTOPHER
Published: June 2012

An electron-microscope study of the localization of acetylcholinesterase (AChE) has been made in the main uterine artery of the guinea pig, which is supplied by cholinergic dilator and adrenergic constrictor nerves. Large bundles of nonterminal axons were present in the outer adventitia, and terminal axons, containing numerous vesicles, were scattered through the inner adventitia up to 1µ away from the outer layer of smooth muscle cells. About 50% of these axons were within 0.2µ of a muscle cell; the minimum neuromuscular gap found was 0.05µ. No axons were within the media. The outer membranes of axons stained either heavily or lightly for AChE. These two distinct classes appear to represent cholinergic and noncholinergic axons, respectively. In late pregnancy, all cholinergic terminal axons which contained vesicles and were not separated from the muscle by Schwann or elastic tissue were associated with heavy postsynaptic staining which was restricted to that region of the muscle membrane adjacent to the axon. In tissue from virgin animals, most cholinergic terminal axons were associated with only scanty postsynaptic staining. The increase in postsynaptic AChE during pregnancy can be correlated with the increase in sensitivity of the arterial muscle to acetylcholine over this period. Assuming that the association of heavy AChE staining both pre- and postsynaptically is indicative of a functional cholinergic synapse, acetylcholine released up to 1µ away from the muscle may participate in transmission from vasodilator axons in this vessel. Since postsynaptic AChE staining is restricted to discrete areas on the outer muscle cells, probably only these cells are directly affected by transmitter released from nerves.
Distribution of Norepinephrine in the Failing Bovine Heart
Authors: VOGEL JOHN H. , JACOBOWITZ DAVID , CHIDSEY CHARLES A.
Published: June 2012

Studies were carried out during experimental heart failure induced in calves to compare the depletion of cardiac norepinephrine in the failing heart to the histochemical appearance of the adrenergic innervation in this tissue. A correlation has been established between the reduction of norepinephrine concentration and the changes in the distribution of the adrenergic neurotransmitter in the tissues. Absence of fluorescence in terminal varicose fibers in close association with cardiac muscle cells was characteristic of the failing heart. Little or no change occurred in preterminal fibers or in terminal fibers in connective tissue septa or around blood vessels. In two steers, recovery from heart failure was shown to be associated with a virtual restoration of the norepinephrine concentration and of thehistochemical appearance of the adrenergic nerve distribution in 28 days or less. These findings suggest that a reversible abnormality, possibly of neurotransmitter storage or synthesis, or both, is induced in the terminal portion of the cardiac adrenergic innervation as the result of the development of the failure state.
Sodium Recovery from Normal and Edematous Lungs Studied by Indicator Dilution Curves
Authors: PEARCE MORTON LEE , Beazell James , Yamashita Joe , Ashcraft Sandra Jill
Published: June 2012

We attempted to measure sodium and water spaces in the lungs before and after pulmonary edema produced in dogs by increasing pulmonary capillary pressure or by alloxan. We employed a technique depending on the difference in transit times through the lungs of tritiated water or
24
Na
+
, with reference to an intravascular indicator. In the control measurements, there was virtually complete recovery of the sodium indicator, but in pulmonary edema there was a significant loss. It is possible that this represents distribution of some of the
24
Na
+
into an extravascular volume with an exit other than the pulmonary veins, but we would expect this to be accompanied by an equivalent amount of tritiated water. Since there was complete recovery of tritiated water in pulmonary edema, it seems more likely that the sodium loss represents binding by some extravascular locus and may be related to the extent of alveolar wall injury.
Electrical Potential Distribution Surrounding the Atria during Depolarization and Repolarization in the Dog
Authors: SPACH MADISON S. , KING TERRY D. , BARR ROGER C. , BOAZ DAVID E. , MORROW MARY N. , HERMAN-GIDDENS SCOTT
Published: June 2012

The potential distribution at the atrial surface during depolarization and repolarization was studied in intact dogs. A preparation was developed by implanting 30 to 40 miniature electrodes permanently on each atrium to record unipolar electrograms in the intact animal. Heart block was created to dissociate atrial and ventricular activity. The electrograms were recorded on magnetic tape and atrial isopotential heart maps produced with the use of a digital computer. The changing potential distribution during excitation indicated the early presence of multiple wave fronts which were related primarily to the crista terminalis, Bachmann's bundle, and a special bundle to the base of the right appendage. The interatrial septum provided a conducting bridge which had an important influence of global atrial excitation, depending on the site of impulse formation. Colliding excitation wave fronts were quite prominent. During terminal atrial excitation, repolarization maxima were present simultaneously with depolarization maxima. Repolarization was characterized by a changing potential distribution which followed the same general pattern as excitation spread; and, furthermore, the earliest areas of excitation were associated with a repolarization maximum and terminal areas of excitation were associated with repolarization minima.
Influence of Glucose on the Transmembrane Action Potential of Guinea-Pig Papillary Muscle
Authors: PRASAD K. , MACLEOD DON P.
Published: June 2012

In a previous report, we have proposed that anaerobic glycolysis alone can maintain an action potential of normal duration in guinea-pig papillary muscle. This proposal followed from the observation that 50 mM glucose, several sympathomimetic amines, and aminophylline all caused the duration of the action potential of muscles, which had been reduced by incubation in a medium containing 5 mM glucose, to return toward control values. This occurred in the presence or absence of oxygen. It was further proposed that the ATP resulting from anaerobic glycolysis was in some way preferentially utilized in the membrane by a process controlling repolarization and therefore the duration of the action potential. The present experiments were undertaken to determine what metabolic pathways were necessary for the glucose effect mentioned above, by the use of the metabolic inhibitors sodium cyanide, iodoacetic acid, and 2,4-dinitrophenol. Secondly, the effects of ouabain and calcium, which are known to modulate the utilization of ATP, on the glucose effect were studied. It was concluded that an intact glycolytic pathway is necessary for the effect of glucose on the electrical activity of papillary muscle and that the effect can be increased or decreased by low or high doses of ouabain, respectively. The actions of ouabain are thought to be due to a stimulation and depression of a membrane ATP-ase.
Peripheral Vascular Response to Simulated Hemorrhagic Shock during Cardiopulmonary Bypass in Dogs
Authors: LONGNECKER DAVID , ABEL FRANCIS L.
Published: June 2012

The peripheral vascular response to hemorrhagic hypotension was examined in thirteen anesthetized dogs on cardiopulmonary bypass. Nine animals were subjected to 2 or 4 hours of hypotension by decreasing pump output (30ml/kg/min), thereby controlling mean arterial blood pressure at 40 mm Hg. Systemic flow was then returned to prehypotensive levels (100 ml/kg/min), and the animals were observed for 6 more hours. Dynamic venous compliance was determined by occluding the venous outflow catheters and recording the venous pressure rise at a known rate of inflow. Venous compliance, changes in reservoir fluid volume, total peripheral resistance, and mean arterial blood pressure were measured at 30-minute intervals. During the first hour of hypotension there was a marked increase in venous compliance, a decrease in reservoir fluid volume, and an increase in total peripheral resistance. Fluid uptake increased during the first hour after returning flow to control values, although mean arterial blood pressure, venous compliance, and total peripheral resistance were similar to the controls during the posthypotensive period. Three dogs were subjected to the same procedure, but without hypotension, to determine the influence of extracorporeal circulation on dynamic compliance when flow is constant. The results indicate that the dog on cardiopulmonary bypass responds to hypotension by arterial constriction and an increase in venous compliance. There was no evidence to indicate a loss of venous or arterial tone within 6 hours following the period of hypotension, although the gross changes in the gut at autopsy were similar to those seen in dogs dying in hemorrhagic shock.
Mechanism of Action of Epinephrine and Glucagon on the Canine Heart: EVIDENCE FOR INCREASE IN SARCOTUBULAR CALCIUM STORES MEDIATED BY CYCLIC 3',5'-AMP
Authors: Entman Mark L. , Levey Gerald S. , Epstein Stephen E.
Published: June 2012

The mechanisms by which the catecholamines and glucagon increase myocardial contractility were investigated by studying the effects of cyclic 3', 5'-AMP, epinephrine, and glucagon on calcium accumulation by a microsomal fraction of canine myocardium thought to represent sarcoplasmic reticulum, and by assaying the microsomal fraction for adenyl cyclase activity. Each agent produced a concentration-dependent increase in calcium accumulation. Moreover, adenyl cyclase, an enzyme activated by epinephrine and glucagon and responsible for the production of cyclic 3', 5'-AMP, was present in the microsomal fraction. Its specific activity and responsiveness to epinephrine and glucagon were similar to that previously found in sarcolemmic fractions. The beta-receptor blocking agent propranolol abolished the activation of adenyl cyclase and increase in microsomal calcium accumulation produced by epinephrine, but was without effect when these same changes were produced by glucagon. These findings are consistent with the hypotheses that: (1) the positive inotropic effects of epinephrine and glucagon may occur as a result of an augmentation of the sarcotubular calcium pool(s); and (2) this effect is mediated, at least in part, by an elevation of cyclic 3', 5'-AMP levels produced by activation of an adenyl cyclase localized to the sarcoplasmic reticulum.
Structural and Functional Characterization of Dog Heart Microsomes
Authors: Pretorius Petrus J. , Pohl W. Gerhard , Smithen Charles S. , Inesi Giuseppe
Published: June 2012

Several procedures for the preparation of microsomes from heart tissue were compared. Sucrose was found the most effective addition to preserve the activity of the sarcoplasmic reticulum vesicles.

Electron microscopy of sectioned pellets shows uniform vesicles, but negative staining of microsomal suspensions allows recognition of mitochondrial fragments, which are found in cardiac microsomal fractions in greater amounts than in skeletal muscle preparations. The quantity of mitochondrial contaminations in different fractions was estimated by measuring enzymatic activities.

A comparison of Ca
2+
accumulation, Ca
2+
efflux, and ATPase activity shows identical features in preparations from the heart and from skeletal muscle, although the specific activity is approximately ten times lower in those from the heart. The apparent affinity of sarcoplasmic reticulum for Ca
2+
in vitro justifies the assumption that sarcoplasmic reticulum lowers the intracellular Ca
2+
concentration in the in-vivo heart below the level required for contraction. However, in a weight unit of fresh tissue, the ratio between the maximal Ca
2+
accumulated by SR and the amount of contractile protein is much lower in the heart than in skeletal muscle.

Caffeine and, more markedly, propranolol and tetracaine increase efflux of accumulated Ca
2+
and thereby reduce net uptake by fragmented sarcoplasmic reticulum. Isopropylmethoxamine is not effective at millimolar concentrations.
Ventricular Function Curves in the Exercising Dog
Authors: KEROES JONATHAN , ECKER ROGER R. , RAPAPORT ELLIOT
Published: June 2012

Ventricular function curves of cardiac output and stroke volume versus left ventricular end-diastolic pressure were obtained during rapid infusion of Tyrode's solution in dogs standing at rest and during near-maximal exercise both before and after administration of propranolol. Cardiac output and stroke volume ventricular function curves were expressions of first-order processes as indicated by the close fit of data points to computer-derived exponential curves. At near-maximal levels of exercise, the rapid infusion of Tyrode's solution increased stroke volume by an average of 12 ml, indicating that at near-maximal exercise the pumping ability of the heart may be limited by venous return rather than by ventricular performance. The heightened sympathetic activity during exercise increased myocardial contractility, since the plateaus of the ventricular function curves were significantly higher during exercise than at rest. Propranolol negated the increase in contractility associated with exercise and the plateaus of ventricular function curves were then not significantly different from those obtained at rest.